8QQF

TBC1D23 PH domain complexed with STX16 TLY motif

Summary for 8QQF

• Entry DOI: 10.2210/pdb8qqf/pdb
• Descriptor: TBC1 domain family member 23, Syntaxin-16, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: tether, vesicle-coat, endosome to golgi transport, snare, endocytosis
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 31899.13

Authors

Kaufman, J.G.,Owen, D.J. (deposition date: 2023-10-04, release date: 2024-04-10)

Primary citation

Cattin-Ortola, J.,Kaufman, J.G.G.,Gillingham, A.K.,Wagstaff, J.L.,Peak-Chew, S.Y.,Stevens, T.J.,Boulanger, J.,Owen, D.J.,Munro, S.
Cargo selective vesicle tethering: The structural basis for binding of specific cargo proteins by the Golgi tether component TBC1D23.
Sci Adv, 10:eadl0608-eadl0608, 2024

PubMed Abstract: The Golgi-localized golgins golgin-97 and golgin-245 capture transport vesicles arriving from endosomes via the protein TBC1D23. The amino-terminal domain of TBC1D23 binds to the golgins, and the carboxyl-terminal domain of TBC1D23 captures the vesicles, but how it recognizes specific vesicles was unclear. A search for binding partners of the carboxyl-terminal domain unexpectedly revealed direct binding to carboxypeptidase D and syntaxin-16, known cargo proteins of the captured vesicles. Binding is via a threonine-leucine-tyrosine (TLY) sequence present in both proteins next to an acidic cluster. A crystal structure reveals how this acidic TLY motif binds to TBC1D23. An acidic TLY motif is also present in the tails of other endosome-to-Golgi cargo, and these also bind TBC1D23. Structure-guided mutations in the carboxyl-terminal domain that disrupt motif binding in vitro also block vesicle capture in vivo. Thus, TBC1D23 attached to golgin-97 and golgin-245 captures vesicles by a previously undescribed mechanism: the recognition of a motif shared by cargo proteins carried by the vesicle.

PubMed: 38552021
DOI: 10.1126/sciadv.adl0608

Experimental method

X-RAY DIFFRACTION (2.19 Å)