How myosin motors power cellular functions – an exciting journey from structure to function

• Published in: The FEBS journal 2012-02, Vol.279 (4), p.551-562
• Main Authors: Llinas, Paola, Pylypenko, Olena, Isabet, Tatiana, Mukherjea, Monalisa, Sweeney, H. Lee, Houdusse, Anne M.
• Format: Article
• Language: English
• Subjects: Cellular biology; chemo‐mechanical transduction; dimerisation; directionality; force production; intra‐cellular transport; Life Sciences; Molecular biology; molecular motor; myosin; Proteins
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2011.08449.x

Molecular motors such as myosins are allosteric enzymes that power essential motility functions in the cell. Structural biology is an important tool for deciphering how these motors work. Myosins produce force upon the actin‐driven conformational changes controlling the sequential release of the hydrolysis products of ATP (Pi followed by ADP). These conformational changes are amplified by a ‘lever arm’, which includes the region of the motor known as the converter and the adjacent elongated light chain binding region. Analysis of four structural states of the motor provides a detailed understanding of the rearrangements and pathways of communication in the motor that are necessary for detachment from the actin track and repriming of the motor. However, the important part of the cycle in which force is produced remains enigmatic and awaits new high‐resolution structures. The value of a structural approach is particularly evident from clues provided by the structural states of the reverse myosin VI motor. Crystallographic structures have revealed that rearrangements within the converter subdomain occur, which explains why this myosin can produce a large stroke in the opposite direction to all other myosins, despite a very short lever arm. By providing a detailed understanding of the motor rearrangements, structural biology will continue to reveal essential information and help solve current enigma, such as how actin promotes force production, how motors are tuned for specific cellular roles or how motor/cargo interactions regulate the function of myosin in the cell. Myosins are molecular motors that power essential motility functions in the cell, and structural biology is an important tool to decipher how these motors work. Functional and structural studies have provided detailed understanding of the motor rearrangements that allow conversion of chemical energy into force production. In particular, studies on a reverse motor have been very insightful since they solved a number of puzzling and controversial enigmas about how this motor produces force, extends its lever arm and dimerizes.