Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex
Year: 2017
Type: article
Abstract: The 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.
Source: eLife
DOI: 10.7554/elife.27322
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: U.S. Department of Energy, Welch Foundation, University of Chicago, University of Texas Southwestern Medical Center, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Biological and Environmental Research, Argonne National Laboratory
OpenAlex ID: W2620106353