Cargo selective vesicle tethering: The structural basis for binding of specific cargo proteins by the Golgi tether component TBC1D23

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 u...

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Published in:Science advances 2024-03, Vol.10 (13), p.eadl0608-eadl0608
Main Authors: Cattin-Ortolá, Jérôme, Kaufman, Jonathan G G, Gillingham, Alison K, Wagstaff, Jane L, Peak-Chew, Sew-Yeu, Stevens, Tim J, Boulanger, Jérôme, Owen, David J, Munro, Sean
Format: Article
Language:English
Subjects:
Biological Transport
Biomedicine and Life Sciences
Cell Biology
Endosomes - metabolism
Golgi Apparatus - metabolism
Golgi Matrix Proteins - metabolism
Membrane Proteins - metabolism
Protein Binding
SciAdv r-articles
Structural Biology
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Summary: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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.adl0608