title: How myosin motors power cellular functions: an exciting journey from structure to function: based on a lecture delivered at the 34th FEBS Congress in Prague, Czech Republic, July 2009.
abstract: 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.
authors.affiliation: Structural Motility, Institut Curie CNRS, Paris, France.
authors.forename: Paola
authors.initials: P
authors.lastname: Llinas
authors.forename: Olena
authors.initials: O
authors.lastname: Pylypenko
authors.forename: Tatiana
authors.initials: T
authors.lastname: Isabet
authors.forename: Monalisa
authors.initials: M
authors.lastname: Mukherjea
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.forename: Anne M
authors.initials: AM
authors.lastname: Houdusse
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D002468:Cell Physiological Phenomena; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000199:Actins; D002147:Calmodulin; D020409:Molecular Motor Proteins; C089785:myosin VI; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D018995:Myosin Heavy Chains; D002118:Calcium