6TL0

Solution structure and 1H, 13C and 15N chemical shift assignments for the complex of VPS29 with VARP 687-747

Summary for 6TL0

• Entry DOI: 10.2210/pdb6tl0/pdb
• NMR Information: BMRB: 34461
• Descriptor: Vacuolar protein sorting-associated protein 29, Ankyrin repeat domain-containing protein 27, ZINC ION (3 entities in total)
• Functional Keywords: varp, retromer, nmr complex structure, zinc finger, endosome, intracellular vesicle trafficking
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 28012.17

Authors

Owen, D.J.,Neuhaus, D.,Yang, J.-C.,Crawley-Snowdon, H. (deposition date: 2019-11-29, release date: 2020-10-21, Last modification date: 2024-05-15)

Primary citation

Crawley-Snowdon, H.,Yang, J.C.,Zaccai, N.R.,Davis, L.J.,Wartosch, L.,Herman, E.K.,Bright, N.A.,Swarbrick, J.S.,Collins, B.M.,Jackson, L.P.,Seaman, M.N.J.,Luzio, J.P.,Dacks, J.B.,Neuhaus, D.,Owen, D.J.
Mechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29.
Nat Commun, 11:5031-5031, 2020

PubMed Abstract: VARP and TBC1D5 are accessory/regulatory proteins of retromer-mediated retrograde trafficking from endosomes. Using an NMR/X-ray approach, we determined the structure of the complex between retromer subunit VPS29 and a 12 residue, four-cysteine/Zn microdomain, which we term a Zn-fingernail, two of which are present in VARP. Mutations that abolish VPS29:VARP binding inhibit trafficking from endosomes to the cell surface. We show that VARP and TBC1D5 bind the same site on VPS29 and can compete for binding VPS29 in vivo. The relative disposition of VPS29s in hetero-hexameric, membrane-attached, retromer arches indicates that VARP will prefer binding to assembled retromer coats through simultaneous binding of two VPS29s. The TBC1D5:VPS29 interaction is over one billion years old but the Zn-fingernail appears only in VARP homologues in the lineage directly giving rise to animals at which point the retromer/VARP/TBC1D5 regulatory network became fully established.

PubMed: 33024112
DOI: 10.1038/s41467-020-18773-2

Experimental method

SOLUTION NMR