5v6e
From Proteopedia
Crystal structure of Myosin VI in complex with GH2 domain of GIPC1
Structural highlights
Disease[MYO6_MOUSE] Note=Defects in Myo6 are the cause of Snell's waltzer, a condition characterized by circling, head-tossing, deafness and hyperactivity. Function[GIPC1_MOUSE] Inhibits endothelial cell migration (in vitro). May be involved in G protein-linked signaling (By similarity). [MYO6_MOUSE] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells. Publication Abstract from PubMedThe GIPC family adaptor proteins mediate endocytosis by tethering cargo proteins to the myosin VI motor. The structural mechanisms for the GIPC/cargo and GIPC/myosin VI interactions remained unclear. PlexinD1, a transmembrane receptor that regulates neuronal and cardiovascular development, is a cargo of GIPCs. GIPC-mediated endocytic trafficking regulates PlexinD1 signaling. Here, we unravel the mechanisms of the interactions among PlexinD1, GIPCs and myosin VI by a series of crystal structures of these proteins in apo or bound states. GIPC1 forms a domain-swapped dimer in an autoinhibited conformation that hinders binding of both PlexinD1 and myosin VI. PlexinD1 binding to GIPC1 releases the autoinhibition, promoting its interaction with myosin VI. GIPCs and myosin VI interact through two distinct interfaces and form an open-ended alternating array. Our data support that this alternating array underlies the oligomerization of the GIPC/Myosin VI complexes in solution and cells. Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex.,Shang G, Brautigam CA, Chen R, Lu D, Torres-Vazquez J, Zhang X Elife. 2017 May 24;6. pii: e27322. doi: 10.7554/eLife.27322. PMID:28537552[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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