Urry D.W. (Ed.) What Sustains Life? : Consilient Mechanisms for Protein-Based Machines and Materials

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8.5 The Myosin II Motor of Muscle Contraction, a Representative ATPase

425

8.5.2.1 Rigor States Substantiate

Hydrophobic Association in Muscle at

the Gross Anatomical Level

As considered in Chapter 7, Borland's Medical

Dictionary has four entries for "rigor."^^ Alpha-

betically listed, they are (1) acid rigor, "coagu-

lation of protein of muscle produced by acids,"

explained by the protonation of carboxylates to

form the uncharged carboxyl, that is, -COO" 4-

H^ = -COOH with the result of contraction

by hydrophobic association; (2) calcium rigor,

"systolic cardiac arrest caused by an excess of

calcium," whereby calcium ion pairing with

paired carboxylates in the presence of hydro-

phobic residues also drives the contraction by

hydrophobic association; (3) heat rigor "rigidity

of muscles induced by heat," explained by the

fundamental property of the consiUent mecha-

nism whereby raising the temperature drives

contraction by hydrophobic association; and (4)

rigor mortis, "the stiffening of a dead body,

accompanying the depletion of adenosine

triphosphate in the muscle fibers," whereby the

suppleness of hydrophobic dissociation in the

presence of the very polar ATP molecule dis-

appears on breakdown of ATP following death

that results in the stiffness of hydrophobic

association.

8.5.2.2 Coherence of Phenomena Relating

to Hydrophobic Association in the

Myofibril and in Elastic-contractile

Model Proteins

8.5.2.2.1

Thermal Activation of

Muscle Contraction

Raising the temperature to drive contraction

by hydrophobic association is the fundamental

property of the consilient mechanism as demon-

strated in Chapter 5 by means of designed

elastic-contractile model proteins. Thermal acti-

vation of muscle contraction also correlates

with contraction by hydrophobic association,

but assisted in this case by the thermal instabil-

ity of phosphoanhydride bonds associated with

ATP,

which on breakdown most dramatically

drive hydrophobic association. In particular,

both muscle and cross-linked elastic protein-

based polymer, (GVGVP)n contract on raising

the temperature over the same temperature

range. Furthermore, there is the corollary of the

release of heat on stretching both muscle

and elastic-contractile model proteins. Both are

exothermic on stretching due to exposure of

hydrophobic groups to water, as may be argued

from the original studies of Butler^^ in 1937.

8.5.2.2.2

Calcium Ion, pH, and Stretch

Activation of Muscle Contraction

At the level of the myofibril, the addition of

calcium ion, the lowering of pH, and stretching

have each been shown to activate muscle con-

traction as well as to drive contraction of suit-

ably designed elastic contractile protein-based

polymers by hydrophobic association (see more

extensive discussion in Chapter 7).

8.5.2.2.3

Dephosphorylation Drives

Contraction, Whereas ATP Binding

Drives Relaxation

Because the energy for contraction comes from

ATP,

original expectations were that ATP and

hydrolysis binding would cause contraction.

TTiis turned out not to be the case. Phosphory-

lation in its many forms causes relaxation by

raising the temperature for the onset of an

inverse temperature transition above physio-

logical temperature, and dephosphorylation

drives contraction exactly in parallel with the

designed elastic-contractile model proteins. In

the latter case, phosphorylation has been shown

to cause relaxation by disrupting hydrophobic

association, and dephosphorylation drives

contraction by allowing re-estabhshment of

hydrophobic association. The very same phe-

nomenological correlations are discussed

below at the molecular level for the myosin II

motor.

8.5.2.2.4 Scenario of Muscle Contraction by

the Inverse Temperature Transition of

Hydrophobic Association

Whether at the anatomical level with the phe-

nomenon of rigor or at the myofibril level with

the variables of physiology, an extensive coher-

ence of phenomena exists. Now we address the

myosin II motor at the molecular level to deter-

426

8. Consilient Mechanisms for Protein-based Machines of Biology

mine if indeed muscle contraction may be

explained in terms of the consilient mechanism

of hydrophobic association under the control of

a competition for hydration between polar (e.g.,

charged) and apolar (hydrophobic) groups. In

this case the common functional groups capable

of existing in different degrees of polarity

would be ADP^- Mg^^ HPOl"; ATP""- Mg'^;

HPOf;

ADP^- Mg'n -COO"; -COO" Me^; and

-COOH, listed in approximate decreasing

order of polarity.

8.5.3 Consideration of Muscle

Contraction at the Molecular Level

8,5,3,1 Approach to the Molecular Level

In the context of relevance of the consilient

mechanism to function of the myosin II motor,

remarkable points are the location and orien-

tation of ATP molecules bound to the cross-

bridge and access to control hydrophobic

associations/dissociations. As considered below

in section 8.5.4.2, narrow clefts function as

conduit through which forces arising from the

polar phosphates are directed at a target site.

In this section on the myosin II motor, coher-

ence of phenomena with that of the consilient

mechanisms of energy conversion is addressed

at the molecular level. Specifically, the impor-

tance of hydrophobic interactions is noted, as

has been generally appreciated. More to the

point, the presence of the apolar-polar repulsive

free energy of hydration appears as a prominent

factor in the contraction/relaxation cycle, and

this has not been previously appreciated.

We begin with a brief orientation to the

gross structural aspects of striated muscle and

quickly move to the microscopic level where

thick myosin and thin actin filaments are driven

into greater overlap with each other during the

cyclic process of myosin cross-bridge attach-

ment to actin, contraction, and detachment

from actin. Then, in a key surfacing of the con-

silient mechanism, we consider the molecular

detail of ATP orientation in its binding site

within the cross-bridge in relation to the

means whereby ATP binding would bring

about detachment of the cross-bridge from the

actin binding site. Next, we consider geometric

relationships of hydrophobic associations and

dissociations relative to ATP binding, hydroly-

sis to form the most polar state of bound ADP

plus Pi, phosphate release, and finally ADP

release. An effort is made to integrate the role

of the calcium ion trigger for muscle contrac-

tion in relation to changing hydrophobic asso-

ciations attending the contraction/relaxation

cycle. Finally, we consider the thermodynamic

efficiency of the myosin II motor in relation to

the development of elastic forces during con-

traction/relaxation and note the substantial

energy requirement of the essential calcium ion

trigger in the contraction/relaxation cycle.

8.5.3.2 Structure of Striated Muscle and

the Sliding Filament Mechanism of

Muscle Contraction

A striated muscle, such as the biceps, is com-

prised of bundles of muscle fibers. The funda-

mental unit of a muscle fiber is the myofibril

composed of a series of repeating units called

sarcomeres defined by the periodicity of Z fines

(disks) at repeat distances of just over 2|im

(e.g., 2.3|Lim). The structural relationships pro-

ceeding from the anatomical level of the biceps

to the microscopic level of the sarcomere are

shown in Figures 8.43,^^ 8.44,^^ and 8.45.^^

FIGURE 8.44. Drawing of a muscle fiber containing

six myofibrils with each surrounded by the sar-

coplasmic reticulum that releases calcium ion to

trigger contraction and that pumps calcium ion back

out to allow for the relaxation in preparation for the

next contraction/relaxation

cycle.

Just inside the sar-

colemma of the muscle fiber that surrounds the

bundles of myofibrils are the mitochondria that

supply the ATP required to convert the fiber from a

contracted state to a relaxed but energized state in

wait for the next release of calcium ion for trigger-

ing phosphate release for onset of the next contrac-

tion/relaxation cycle. Also shown is the location of

the Z disk that separates sarcomeres (the funda-

mental unit of muscle contraction) and the arrange-

ment of the A and I bands that are defined in detail

in Figure

8.45.)

(From

Fundamental

of Biochemistry,

John Wiley & Sons, New York. Reprinted with per-

mission of John Wiley & Sons, Inc.)

Muscle

Bundle

muscle

fibers

M \f

Myofibril

^ f P *

Nucler

Individual

muscle

fiber

FIGURE

8.43. Musculature of a man that highlights

the biceps muscle, perhaps best recognized for per-

forming the mechanical work of lifting a weight, with

a cutaway to an individual muscle fiber, presented as

a bundle of myofibrils that contains the fundamental

contractile element. (From Fundamentals of Bio-

chemistry, D. Voet, J. Voet & C.W. Pratt,^^ Copyright

1995,

John Wiley & Sons, New York. Reprinted with

permission of John Wiley & Sons, Inc.)

Sarcotubuies Mitochondrion

Terminal

Myofibrils

Triad

of the

reticulum

band

428

8. Consilient Mechanisms for Protein-based Machines of Biology

FIGURE 8.45. (Top) Electron micrograph of a

myofibril delineating the A and I bands, the Z disk,

and the H zone. (Bottom) Schematic representation

of a microfibril showing thin actin filaments emanat-

ing from Z disks and overlapping with thick myosin

•*iV4%

Transverse

•:•>:•

sections

filaments to form part of the A band and with myosin

filaments occurring alone in the region of the H zone.

Four transverse sections at indicated sites show

packing of actin and myosin filaments. (Reproduced

with permission from Voet et al.^^)

Emanating from the Z lines are thin actin fil-

aments, and between the thin actin filaments,

and generally overlapping only partially, are

thick myosin filaments that contact the actin fil-

aments by means of cross-bridges. Contraction

results as the thick myosin filaments drive into

greater overlap with the thin actin filaments

due to the ATP-driven action of the cross-

bridges.^^'^^^ This sliding filament by cross-

bridge action decreases the distance between Z

lines and constitutes contraction by shortening

of the muscle fibers. Preparations of the cross-

bridges are variously referred to as the myosin

subfragment'l (SI) and the myosin

head.

8.5.3,3 Swinging Cross-bridge

Representation of the Myosin II

Contraction/Relaxation Cycle

A common perspective of the contraction/

relaxation cycle comes from the text of Voet et

al.,^^^

as shown in Figure 8.46. An illustration at

the top of Figure 8.46 shows the thick myosin

filament between thin actin filaments with glob-

ular cross-bridges directed from the myosin

filament toward the thin actin filaments. The

sliding filament model has the cyclic attach-

ment-contraction/detachment-relaxation

action of the cross-bridges driving the thick

8.5 The Myosin II Motor of Muscle Contraction, a Representative ATPase 429

filament further into overlap with the thin fila-

ments and resulting in the ends of the thin fila-

ments moving toward each other. Again, this

motion shortens the distance between Z lines

that defines the fundamental unit of muscle

contraction, the sarcomere, and results in the

shortening of the muscle fiber that constitutes

muscle contraction.

•• M disk

1 ATP binds to Sl head;

actin cleft opens; Sl head

releases actin

4 p. release resulting

In strong binding of

Sl head to actin

FIGURE 8.46. Contraction cycle in a swinging

cross-bridge representation for the myosin II motor

showing the cross-bridge performing a rowing-like

motion. This rendering of the contraction/relaxation

cycle begins with the cross-bridge attached to the

actin filament. ATP binding induces detachment.

Formation of ADP«Pi induces forward extension. Pi

release yields firm re-attachment to the actin fila-

ment and results in the powerstroke for contraction.

This is followed by ADP release in readiness for the

next cycle to begin again with ATP binding. A coor-

dinate system has been added at lower right in which

the positive X-axis takes the direction of the myosin

filament pointing away from the site where a cross-

Active site closure 1 ^^

followed by ATP Y^^

hydrolysis causing f

cocking of

head X

"T*

3 Weak binding of

Sl head to actin

H2O

"Y-axis

i ^-'

Z-axis

out of plane

bridge emerges; the Y-axis approximates the direc-

tion of the a-helical lower segment of the lever arm

in the direction of the actin filament, and the Z-axis

is out of the

plane.

The

cross-bridge structures exam-

ined in subsequent figures are viewed approximately

with the three projections in the three planes, YZ,

XY, and XZ, but in stereo projection in each case to

give the third

dimension.

These three projections are

given in Figures 8.47 through 8.52 using initially the

space-filling representation followed by either back-

bone or ribbon representations. (From Biochemistry,

Voet and

Voet,^^

(1995,

John Wiley

& Sons, New York). Reprinted with permission of

John Wiley & Sons, Inc.)

430

8. Consilient Mechanisms for Protein-based Machines of Biology

In the expanded view of cross-bridge-actin

interaction of Figure 8.46, step 1, the binding

of ATP to the cross-bridge causes detachment

of cross-bridge from the actin filament. Step 2

is the hydrolysis of bound ATP to yield

bound ADP plus bound phosphate. This occurs

with the forward movement of the cross-bridge

(as in the moving forward of an oar) along

the actin filament and with re-estabUshment of

a weak interaction of the cross-bridge with

actin as step 3. Release of phosphate as step 4

results in the combined strong binding of cross-

bridge to actin immediately followed by the

powerstroke. Step 5 represents the sUding of

the thick filament further into the array of thin

filaments. With release of ADP as step 6, the

cross-bridge-actin interaction returns to the sit-

uation before ATP binding, thereby completing

the cycle. In what follows, these steps will be

considered in terms of detailed molecular inter-

actions with emphasis on the consiUent mecha-

nism involving the apolar-polar repulsive free

energy of interaction and its relationship to

controlling hydrophobic hydration and hydro-

phobic association.

8.5.3.3.1

Analyses of Crystal Structures Below

Do Not Support the Bending Motion of the

Cross-bridge as Depicted in Figure 8.46

As shown below in Figures 8.47 through 8.52,

which compare the different axial projections

of the near-rigor and nucleotide bound states,

there is no bending motion as illustrated in the

results of steps 2 and

The contraction appears

as a more complex motion involving a twisting

within the lower part of the globular portion of

the cross-bridge that changes the direction at

which the single a-helix of the lever arm

leaves the globular component. Rather than

being strengthened by a-helical multistranding

of the lever arm, it would appear that the

essential and regulatory Ught chains fulfill such

a re-enforcement role.

8.5.3.3.2

Absence in Figure 8.46 of Including

Calcium Ion Release as the Event That

Triggers Contraction

Another critical element in the contraction/

relaxation cycle is to position the point of

calcium ion release that provides the in vivo

trigger for the contractile event. This will be

considered in relation to details of an interplay

of hydrophobic dissociations/associations that

attend the contractile process.

8.5.4 Crystal Structure Analyses and

Consilient Mechanisms in the

Myosin II Motor

The crystal structure analyses utilize two crystal

structures of the myosin II motor of scallop

muscle available from the Protein Data Bank

(http://www.rcsb.org/pdb) as Structure Files

1KK7 and 1KK8.^ Structure 1KK7 is a near-

rigor state with a sulfate at the active site, and

structure 1KK8 is a nucleotide-containing state

with ADP-BeFx (where BeFx is an analogue

for the y-phosphate) at the active

site.

The illus-

trations utilize FrontDoor to Protein Explorer

which can be obtained at no cost at www.

proteinexplorer.org. All structures are repre-

sented in shades of gray spanning from black

for aromatic residues, gray for other hydro-

phobic residues, light gray for neutral residues,

and white for charged residues, as fits with the

deUneation of polar (charged) as white and

apolar varying from gray to black. In this way

apolar regions can be distinguished at a glance

from polar (charged) regions, with oil-Hke

hydrophobic domains seen as dark regions and

with polar domains seen as white regions. This

allows immediate recognition of the location,

size,

and intensity of hydrophobic domains. The

only exception to this coding scheme is in

Figure 8.47, where the shades of gray are used

to delineate the three different chains of the

cross-bridge.

8.5.4.1 Structural Composition of the

Myosin Cross-bridge

The structures used here contain that part of

the amino terminus of myosin (residues 1 to

835) just sufficient to include the essential and

regulatory light chains. Thus, the cross-bridge is

composed of three chains—approximately 800

residues from the amino terminus of the myosin

chain, the essential light chain, and the regula-

8.5 The Myosin II Motor of Muscle Contraction, a Representative ATPase

431

onverter

domain

N-termin

domain

^iEssential

Ij^ht chain

Regulator}

light chain

SOkDa

upp

FIGURE 8.47. Stereo view (cross-eye) in space-filling

representation of the scallop muscle cross-bridge

(SI) in gray, with the essential light chain in white

and the regulatory light chain in light

gray.

The coor-

dinate system is chosen with the foot of the lever arm

(obscured by the regulatory light chain) pointing in

the direction of the myosin filament from which it

arises.

Accordingly, this is a projection on the YZ

plane looking in the negative X-direction before the

approximate 90° kink in the a-heUcal lever arm that

TP-analogue

X-axis is out

the

plane and

parallel to the

myosin filament

Z-axis

connects the globular portion of the cross-bridge to

the myosin filament. This alignment of the axes is

better seen in Figures 8.48, 8.50, and 8.52. (A) Near-

rigor state. (Prepared using the crystallographic

results of Himmel et al.^ as obtained from the

Protein Data Bank, Structure File 1KK7.) (B) ATP

analogue state (ADP-BeFx). (Prepared using the

crystallographic results of Himmel et al.^ as obtained

from the Protein Data Bank, Structure File 1KK8.)

tory light chain. The myosin sequence within

the cross-bridge includes the lever arm that

connects the globular portion of the cross-

bridge to the myosin filament, which a-helical

sequence is decorated at the filament end with

the regulatory chain and at the globular end

with the essential light chain. The globular

portion of the cross-bridge is divided into a set

of domains: the amino-terminal domain that we

point to below as important in the hydrophobic

432

8. Consilient Mechanisms for Protein-based Machines of Biology

association associated with the powerstroke, a

50kDa segment divided into upper and lower

domains separated by a cleft that runs from the

nucleotide binding site to the actin binding site,

and a converter domain that resides at the head

of the lever arm that structurally ties to the

lower domain of the 50kDa segment.

8.5.4.2 Early Seminal Contributions of

Rayment and Coworkers and Their

Relationship to the Consilient

Mechanisms

8.5.4.2.1

The Early Insights of Rayment

and Coworkers

In 1993, Rayment and coUeagues^^^'^^^ pub-

lished two seminal papers on the "Three-

dimensional structure of the head portion of

myosin, or subfragment-1, which contains

both the actin and nucleotide-binding sites...."

Thereby, these publications provided key struc-

tural aspects of the contraction/relaxation

cycle. Shortly thereafter in a report of their

structural studies of the myosin head from Dic-

tostelium myosin II, Rayment and coworkers

concluded that "The current structural results

emphasize the importance of the narrow cleft

that splits the 50-kDa segment in the mole-

cular origin of myosin based motility. They

suggest further that it functions not only in

sensing the presence of the y-phosphate of ATP

but is also responsible for transducing the

conformational change that results in the

powerstroke.'"^

8.5.4.2.2

Extensions of the Early Insights of

Rayment and Coworkers by Means of the

Hydrophobic Consilient Mechanism

In what follows, we extend these insights in two

significant ways. One way recognizes that the

"narrow cleft" not only "splits the 50-kDa

segment" in the direction of the binding site

with actin, but also that the "narrow cleft" is

directed toward the junction between the

amino-terminal domain and the head of the

lever arm to, in our view, effect "the conforma-

tional change that results in the powerstroke."

Our second extension is in the nature of the

force emanating from the y-phosphate in both

directions. The force disrupts the hydrophobic

association responsible for attachment to actin

and the hydrophobic association between the

amino-terminal domain and the head of the

lever arm. That force given focus and direction

by the "narrow cleft" derives from the

apolar-polar repulsive free energy of hydra-

tion,

AGap-

AGap

derives from a competition for

hydration between hydrophobic and charged

groups and as such constitutes a repulsive

force that disrupts hydrophobic hydration and

thereby disrupts hydrophobic association.

Hydrolysis of ATP to release the y-phosphate

that leaves the structure, therefore, has two

consequences. Strong hydrophobic association

is re-established between the cross-bridge and

the actin binding site, and strong hydro-

phobic association is re-established between

the amino-terminal domain and the head of the

lever arm to provide the powerstroke. This

perspective resides at the heart of the pro-

posed contribution of the hydrophobic con-

silient mechanism to function of the myosin II

motor. It is considered further below and most

directly in section 8.5.4.7.

8.5.4.2.3

Efficient Energy Transduction

Requires Coupling to Near-ideal Elastic

Force Development

The above perspectives are natural conse-

quences of both the hydrophobic and the

elastic consiHent mechanisms as applied to the

structural data on the myosin II motor. Here we

briefly explore the elastic element. An ideal

elastomer exhibits exactly reversible stress-

strain curves with complete recovery on relax-

ation of the energy of deformation. On the

other hand, an elastomer that exhibits

hysteresis does not recover all of the energy on

relaxation that was expended on deformation.

Accordingly, efficient muscle contraction

should involve the deformation of near-ideal

elastic segments to utilize more efficiently the

energy expended in driving contraction. The

mechanism of elasticity that can provide such

near-ideal elasticity is the damping of internal

chain dynamics on extension.

There are many aspects of the hydrophobic

and elastic consilient mechanisms that warrant

8.5 The Myosin II Motor of Muscle Contraction, a Representative ATPase

433

discussion in relation to the mechanism of

muscle contraction. Limitations of time and

space, however, necessarily restrict considera-

tion of many important aspects of muscle con-

traction that naturally flow from the insight of

these consilient mechanisms. In what follows,

we emphasize the role of the narrow cleft in

terms of the presence and absence of nucleo-

tide phosphates controlling hydrophobic

associations/dissociations by means of the

apolar-polar repulsive free energy of hydra-

tion,

AGap.

Specifically, the hydrophobic associ-

ations/dissociations involve the binding of the

cross-bridge to the actin filament and the

interaction of the amino-terminal domain with

the head of the lever arm to achieve the

powerstroke.

8.5.4.3 The Near-rigor and ATP

(Analogue) Bound States of the

Cross-bridge Compared in Three

Planes Defined by Axes Set at the

Myosin Filament

In setting up the coordinate system, the X-axis

is taken parallel to the axis of the myosin fila-

ment; the Y-axis is taken perpendicular to the

myosin filament in the direction of the actin

filament to which the cross-bridge would

attach, and the Z-axis is approximated by

sighting through the center of the a-helical

sequence of the lever arm involving residues

825 to 800 of scallop muscle.

8.5.4.3.1

View of Complete Cross-bridge

in the YZ Plane Perpendicular to the

Myosin Filament

A space-filling representation of the complete

cross-bridge is shown in Figure 8.47, with the

near-rigor state in A and the state containing

the ATP analogue in B. The 50kDa upper and

lower domains and other domains of the

myosin chain segment, for example, the amino-

terminal domain and the converter domain, are

in gray. Also shown and labeled are the essen-

tial light chain in white and the regulatory light

chain in light gray. The globular head of the

myosin chain, including in particular the amino-

terminal domain, appears to be twisted in a

clockwise direction as seen from the top.

The structural rearrangements appear more

obvious in Figure 8.48, which is the same view

given in backbone representation. The a-helical

lever arm is shown in its entirety from foot to

head with a knee bend at the junction of the

essential and regulatory light chains and with

an essentially unchanged orientation on going

from the near-rigor state to an analogue

representative of the ATP bound state. In

this view the relocation of the amino-terminal

domain is apparent, but becomes clearer in

subsequent perspectives below in Figures 8.50

and 8.52.

8.5.4.3.2

View of the Cross-bridge in the XY

Plane Demonstrates Absence of the Bending

Motion at the Myosin Filament End of

the Lever Arm

The cross-eye stereo view of the myosin cross-

bridge of scallop muscle is given for the near-

rigor state in Figure

8.49A

and in the ATP

analogue state in Figure 8.49B. In this perspec-

tive the amino-terminal domain is shown to

have shifted from the left side of the head of

the lever arm to the righthand side, while the

essential light chain seems to have shifted very

little.

Again, the globular head of the myosin

chain follows the same reorientation as the

amino-terminal domain, exhibiting a clockwise

rotation when seen from above.

Exactly the same perspectives of Figure 8.49

in space-filling representation are given in

ribbon representation in Figure 8.50, which

allows for a clearer view of any structural

rearrangements that occur between near-rigor

and ATP bound states. Again, it appears that

the essential Ught chain changes little but that

the amino-terminal domain, the leading edge of

which is identified by residue G53, undergoes a

large relocation on conversion to the near-rigor

state.

Although there may be a slight change in

the bend at the knee of the a-helical lever arm,

there is no detectable change in the approxi-

mately right angle turn on going from myosin

filament segment to the lever arm. The bending

motions indicated in steps 2 and 5 of Figure 8.46

do not occur.

8. Consilient Mechanisms for Protein-based Machines of Biology

Converter

domain

N-termini

domain

a-helical^

lever arm

^H''-'^^-

50kDa

ATP-analogue

^Regulatory

flight chain

FIGURE 8.48. Stereo view (cross-eye) in backbone

representation of scallop muscle cross-bridge (SI) in

gray,

with the essential and regulatory Ught chains in

Ught gray. Projection on the YZ plane looking in the

negative X-direction before the 90° kink, forming a

foot-like structure where the a-helical lever arm con-

nects to the myosin filament. The a-helical lever arm

exhibits a knee-like bend at the function of the

essential and regulatory light chains midway

between a foot section and the head portion that

Z-axis<—^^j

X-axis is out yv^"^

the

plane

Y-aids

nestles between the converter domain and the

amino-terminal domain in A. (A) Near-rigor state

that contains a single sulfate at the active site. (Pre-

pared using the crystallographic results of Himmel et

al.^

as obtained from the Protein Data Bank, Struc-

ture File 1KK7.) (B) ATP state with ATP analogue

(ADP-BeFx) shown in space-filling representation.

(Prepared using the crystallographic results of

Himmel et al.^ as obtained from the Protein Data

Bank, Structure File 1KK8.)