Roles of singleton tryptophan motifs in COPI coat stability and vesicle tethering.

TitleRoles of singleton tryptophan motifs in COPI coat stability and vesicle tethering.
Publication TypeJournal Article
Year of Publication2019
AuthorsTravis, SM, Kokona, B, Fairman, R, Hughson, FM
JournalProc Natl Acad Sci U S A
Volume116
Issue48
Pagination24031-24040
Date Published2019 11 26
ISSN1091-6490
KeywordsAmino Acid Motifs, Coat Protein Complex I, Conserved Sequence, Crystallography, X-Ray, Endoplasmic Reticulum, Intracellular Membranes, Models, Molecular, Protein Stability, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Tryptophan
Abstract

<p>Coat protein I (COPI)-coated vesicles mediate retrograde transport from the Golgi to the endoplasmic reticulum (ER), as well as transport within the Golgi. Major progress has been made in defining the structure of COPI coats, in vitro and in vivo, at resolutions as high as 9 Å. Nevertheless, important questions remain unanswered, including what specific interactions stabilize COPI coats, how COPI vesicles recognize their target membranes, and how coat disassembly is coordinated with vesicle fusion and cargo delivery. Here, we use X-ray crystallography to identify a conserved site on the COPI subunit α-COP that binds to flexible, acidic sequences containing a single tryptophan residue. One such sequence, found within α-COP itself, mediates α-COP homo-oligomerization. Another such sequence is contained within the lasso of the ER-resident Dsl1 complex, where it helps mediate the tethering of Golgi-derived COPI vesicles at the ER membrane. Together, our findings suggest that α-COP homo-oligomerization plays a key role in COPI coat stability, with potential implications for the coordination of vesicle tethering, uncoating, and fusion.</p>

DOI10.1073/pnas.1909697116
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID31712447
PubMed Central IDPMC6883825
Grant ListP41 GM103485 / GM / NIGMS NIH HHS / United States
P41 GM111244 / GM / NIGMS NIH HHS / United States
R01 GM071574 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States