Myosin-5 varies its step length to carry cargo straight along the irregular F-actin track

被引：2

作者：

Fineberga, Adam ^{[5
,6
]}

Takagi, Yasuharu ^{[7
]}

Thirumurugan, Kavitha ^{[1
,8
,9
]}

Andrecka, Joanna ^{[2
,5
]}

Billingtonc, Neil ^{[3
,7
]}

Young, Gavin ^{[5
]}

Cole, Daniel ^{[4
,5
]}

Burgess, Stan A. ^{[8
,9
]}

Curd, Alistair P. ^{[8
,9
]}

Hammer, John A. ^{[10
]}

Sellers, James R. ^{[3
]}

Kukura, Philipp ^{[5
,11
]}

Knight, Peter J. ^{[8
,9
]}

机构：

[1] Vellore Inst Technol, Sch Bio Sci & Technol, Struct Biol Lab, Pearl Res Pk, Vellore 632014, India

[2] Human Technopole, I-20157 Milan, Italy

[3] West Virginia Univ, Dept Biochem & Mol Med, Morgantown, WV 26506 USA

[4] Refeyn Ltd, Oxford OX4 6FF, England

[5] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England

[6] Natl Heart Lung & Blood Inst, Lab Single Mol Biophys, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA

[7] Natl Heart Lung & Blood Inst, Lab Mol Physiol, Cell & Dev Biol Ctr, Natl Heart, Bethesda, MD 20892 USA

[8] Univ Leeds, Fac Biol Sci, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, England

[9] Univ Leeds, Fac Biol Sci, Sch Mol & Cellular Biol, Leeds LS2 9JT, England

[10] Natl Heart Lung & Blood Inst, Cell & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA

[11] Univ Oxford, Kavli Inst Nanosci Discovery, Dorothy Crowfoot Hodgkin Bldg, Oxford OX1 3QU, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2024年 / 121卷 / 13期

基金：

英国生物技术与生命科学研究理事会; 欧洲研究理事会; 英国惠康基金;

关键词：

myosin-5; actin filament; cumulative angular disorder (CAD); interferometric scattering (iSCAT); myosin microscopy; electron microscopy; HAND-OVER-HAND; NEAR-ATOMIC-RESOLUTION; PROCESSIVE MOVEMENT; OPTICAL-DETECTION; MOLECULAR MOTOR; NECK LENGTH; DYNAMICS; KINETICS; COMPLEX; BINDING;

D O I：

10.1073/pnas.2401625121

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Molecular motors employ chemical energy to generate unidirectional mechanical output against a track while navigating a chaotic cellular environment, potential disorder on the track, and against Brownian motion. Nevertheless, decades of nanometer -precise optical studies suggest that myosin -5a, one of the prototypical molecular motors, takes uniform steps spanning 13 subunits (36 nm) along its F-actin track. Here, we use high -resolution interferometric scattering microscopy to reveal that myosin takes strides spanning 22 to 34 actin subunits, despite walking straight along the helical actin filament. We show that cumulative angular disorder in F-actin accounts for the observed proportion of each stride length, akin to crossing a river on variably spaced stepping stones. Electron microscopy revealed the structure of the stepping molecule. Our results indicate that both motor and track are soft materials that can adapt to function in complex cellular conditions.

引用

页数：12