title: Structural comparisons of muscle and nonmuscle actins give insights into the evolution of their functional differences.
abstract: Actin is a highly conserved protein although many isoforms exist. In vertebrates and insects the different actin isoforms can be grouped by their amino acid sequence and tissue-specific gene expression into muscle and nonmuscle actins, suggesting that the different actins may have a functional significance. We ask here whether atomic models for G- and F-actins may help to explain this functional diversity. Using a molecular graphics program we have mapped the few amino acids that differ between isoactins. A small number of residues specific for muscle actins are buried in internal positions and some present a remarkable organization. Within the molecule, the replacements observed between muscle and nonmuscle actins are often accompanied by compensatory changes. The others are dispersed on the protein surface, except for a cluster located at the N-terminus which protrudes outward. Only a few of these residues specific for muscle actins are present in known ligand binding sites except the N-terminus, which has a sequence specific for each isoactin and is directly implicated in the binding to myosin. When we simulated the replacements of side chains of residues specific for muscle actins to those specific for nonmuscle actins, the N-terminus appears to be less compact and more flexible in nonmuscle actins. This would represent the first conformational grounds for proposing that muscle and nonmuscle actins may be functionally distinguishable. The rest of the molecule is very similar or identical in all the actins, except for a possible higher internal flexibility in muscle actins. We propose that muscle actin genes have evolved from genes of nonmuscle actins by substitutions leading to some conformational changes in the protruding N-terminus and the internal dynamics of the main body of the protein.
authors.affiliation: Centre de Génétique Moléculaire et Cellularire, Université Lyon 1, 43 boulevard du 11 Novembre 1918, 69 622 Villeurbanne, France.
authors.forename: N
authors.initials: N
authors.lastname: Mounier
authors.forename: J C
authors.initials: JC
authors.lastname: Sparrow
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000502:physiology; D000255:Adenosine Triphosphate; D000596:Amino Acids; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D003593:Cytoplasm / Q000737:chemistry; D019143:Evolution, Molecular; D008322:Mammals; D008958:Models, Molecular; D009132:Muscles / Q000737:chemistry*; D009218:Myosins
chemical_list: D000199:Actins; D000596:Amino Acids; D000255:Adenosine Triphosphate; D009218:Myosins