title: Actin-binding proteins--a unifying hypothesis.
abstract: Actin participates in more protein-protein interactions than any other known protein, including the interaction of actin with itself to form the helical polymer F-actin. The vast majority of actin-binding proteins (ABPs) can be grouped into conserved families. Only a handful of structures of complexes of actin with ABPs have been determined so far. These structures are starting to reveal how certain ABPs, including gelsolin, vitamin D-binding protein and Wiskott-Aldrich syndrome protein (WASP)-homology domain-2-related proteins, share a common actin-binding motif. It is proposed here that other ABPs, including actin itself, might share this motif, providing a mechanism whereby ABPs and actin compete for a common binding site. Of particular interest is a hydrophobic pocket that mediates important interactions in five of the existing structures of actin complexes. As the pocket remains accessible in F-actin, it is proposed that this pocket represents a primary target for F-actin-binding proteins, such as calponin-homology-related proteins and myosin.
authors.affiliation: Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA. Dominguez@bbri.org
authors.forename: Roberto
authors.initials: R
authors.lastname: Dominguez
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D051345:Destrin; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018260:Gelsolin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010080:Oxazoles / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014809:Vitamin D-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D051345:Destrin; D029721:Drosophila Proteins; D018260:Gelsolin; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010080:Oxazoles; D011506:Proteins; D014809:Vitamin D-Binding Protein; D051316:Wiskott-Aldrich Syndrome Protein; C414741:cib protein, Drosophila; C489776:kabiramide C