3pzd
Structure of the myosin X MyTH4-FERM/DCC complexStructure of the myosin X MyTH4-FERM/DCC complex
Structural highlights
Function[MYO10_HUMAN] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as plus end-directed motor. The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments. Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. May play a role in neurite outgrowth and axon guidance. Plays a role in formation of the podosome belt in osteoclasts (By similarity).[1] [DCC_MOUSE] Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene. Publication Abstract from PubMedMyosin X (MyoX), encoded by Myo10, is a representative member of the MyTH4-FERM domain-containing myosins, and this family of unconventional myosins shares common functions in promoting formation of filopodia/stereocilia structures in many cell types with unknown mechanisms. Here, we present the structure of the MyoX MyTH4-FERM tandem in complex with the cytoplasmic tail P3 domain of the netrin receptor DCC. The structure, together with biochemical studies, reveals that the MyoX MyTH4 and FERM domains interact with each other, forming a structural and functional supramodule. Instead of forming an extended beta-strand structure in other FERM binding targets, DCC_P3 forms a single alpha-helix and binds to the alphabeta-groove formed by beta5 and alpha1 of the MyoX FERM F3 lobe. Structure-based amino acid sequence analysis reveals that the key polar residues forming the inter-MyTH4/FERM interface are absolutely conserved in all MyTH4-FERM tandem-containing proteins, suggesting that the supramodular nature of the MyTH4-FERM tandem is likely a general property for all MyTH4-FERM proteins. Cargo recognition mechanism of myosin X revealed by the structure of its tail MyTH4-FERM tandem in complex with the DCC P3 domain.,Wei Z, Yan J, Lu Q, Pan L, Zhang M Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3572-7. Epub 2011 Feb 14. PMID:21321230[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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