Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

Guijun Shang, Chad A Brautigam, Rui Chen, Defen Lu, Jesús Torres-Vázquez, Xuewu Zhang

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere27322
JournaleLife
Volume6
DOIs
StatePublished - May 24 2017

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Oligomerization
Proteins
Endocytosis
myosin VI
Dimers
Conformations
Crystal structure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex. / Shang, Guijun; Brautigam, Chad A; Chen, Rui; Lu, Defen; Torres-Vázquez, Jesús; Zhang, Xuewu.

In: eLife, Vol. 6, e27322, 24.05.2017.

Research output: Contribution to journalArticle

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