2J9W

Structural insight into the ESCRT-I-II link and its role in MVB trafficking

Summary for 2J9W

• Entry DOI: 10.2210/pdb2j9w/pdb
• Related: 2J9U 2J9V
• Descriptor: VPS28-PROV PROTEIN (2 entities in total)
• Functional Keywords: nzf finger, hiv budding, protein transport
• Biological source: XENOPUS LAEVIS (AFRICAN CLAWED FROG)
• Total number of polymer chains: 2
• Total formula weight: 24001.39

Authors

Gill, D.J.,Teo, H.L.,Sun, J.,Perisic, O.,Veprintsev, D.B.,Emr, S.D.,Williams, R.L. (deposition date: 2006-11-16, release date: 2007-01-23, Last modification date: 2024-05-01)

Primary citation

Gill, D.J.,Teo, H.,Sun, J.,Perisic, O.,Veprintsev, D.B.,Emr, S.D.,Williams, R.L.
Structural Insight Into the Escrt-I/-II Link and its Role in Mvb Trafficking.
Embo J., 26:600-, 2007

PubMed Abstract: ESCRT (endosomal sorting complex required for transport) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs). Yeast ESCRT-I and ESCRT-II interact directly in vitro; however, this association is not detected in yeast cytosol. To gain understanding of the molecular mechanisms of this link, we have characterised the ESCRT-I/-II supercomplex and determined the crystal structure of its interface. The link is formed by the vacuolar protein sorting (Vps)28 C-terminus (ESCRT-I) binding with nanomolar affinity to the Vps36-NZF-N zinc-finger domain (ESCRT-II). A hydrophobic patch on the Vps28-CT four-helix bundle contacts the hydrophobic knuckles of Vps36-NZF-N. Mutation of the ESCRT-I/-II link results in a cargo-sorting defect in yeast. Interestingly, the two Vps36 NZF domains, NZF-N and NZF-C, despite having the same core fold, use distinct surfaces to bind ESCRT-I or ubiquitinated cargo. We also show that a new component of ESCRT-I, Mvb12 (YGR206W), engages ESCRT-I directly with nanomolar affinity to form a 1:1:1:1 heterotetramer. Mvb12 does not affect the affinity of ESCRT-I for ESCRT-II in vitro. Our data suggest a complex regulatory mechanism for the ESCRT-I/-II link in yeast.

PubMed: 17215868
DOI: 10.1038/SJ.EMBOJ.7601501

Experimental method

X-RAY DIFFRACTION (1.3 Å)