5V6H

Crystal structure of Myosin VI in complex with GH2 domain of GIPC2

Summary for 5V6H

• Entry DOI: 10.2210/pdb5v6h/pdb
• Related: 5V6E 5V6R 5V6T 5V7B
• Descriptor: PDZ domain-containing protein GIPC2, Unconventional myosin-VI (2 entities in total)
• Functional Keywords: binding partener, protein binding
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 10
• Total formula weight: 72546.80

Authors

Shang, G.,Zhang, X. (deposition date: 2017-03-16, release date: 2017-05-31, Last modification date: 2024-03-06)

Primary citation

Shang, G.,Brautigam, C.A.,Chen, R.,Lu, D.,Torres-Vazquez, J.,Zhang, X.
Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex.
Elife, 6:-, 2017

PubMed 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.

PubMed: 28537552
DOI: 10.7554/eLife.27322

Experimental method

X-RAY DIFFRACTION (3.601 Å)