5v6r | pdb_00005v6r
Structure of Plexin D1 intracellular domain
Structural highlights
FunctionPLXD1_MOUSE Cell surface receptor for SEMA4A and for class 3 semaphorins, such as SEMA3A, SEMA3C and SEMA3E. Plays an important role in cell-cell signaling, and in regulating the migration of a wide spectrum of cell types. Regulates the migration of thymocytes in the medulla. Regulates endothelial cell migration. Plays an important role in ensuring the specificity of synapse formation. Mediates anti-angiogenic signaling in response to SEMA3E. Required for normal development of the heart and vasculature.[1] [2] [3] [4] [5] [6] 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[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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