Longin-like folds identified in CHiPS and DUF254 proteins: Vesicle trafficking complexes conserved in eukaryotic evolution

Lisa N. Kinch, Nick V. Grishin

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Eukaryotic protein trafficking pathways require specific transfer of cargo vesicles to different target organelles. A number of vesicle trafficking and membrane fusion components participate in this process, including various tethering factor complexes that interact with small GTPases prior to SNARE-mediated vesicle fusion. In Saccharomyces cerevisiae a protein complex of Mon1 and Ccz1 functions with the small GTPase Ypt7 to mediate vesicle trafficking to the vacuole. Mon1 belongs to DUF254 found in a diverse range of eukaryotic genomes, while Ccz1 includes a CHiPS domain that is also present in a known human protein trafficking disorder gene (HPS-4). The present work identifies the CHiPS domain and a sequence region from another trafficking disorder gene (HPS-1) as homologs of an N-terminal domain from DUF254. This link establishes the evolutionary conservation of a protein complex (HPS-1/HPS-4) that functions similarly to Mon1/Ccz1 in vesicle trafficking to lysosome-related organelles of diverse eukaryotic species. Furthermore, the newly identified DUF254 domain is a distant homolog of the m-adaptin longin domain found in clathrin adapter protein (AP) complexes of known structure that function to localize cargo protein to specific organelles. In support of this fold assignment, known longin domains such as the AP complex σ-adaptin, the synaptobrevin N-terminal domains sec22 and Ykt6, and the srx domain of the signal recognition particle receptor also regulate vesicle trafficking pathways by mediating SNARE fusion, recognizing specialized compartments, and interacting with small GTPases that resemble Ypt7. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)2669-2674
Number of pages6
JournalProtein Science
Volume15
Issue number11
DOIs
StatePublished - 2006

Keywords

  • CHiPs domain
  • Ccz1
  • DUF254
  • Fold recognition
  • HPS-1
  • HPS-4
  • Hermansky-Pudlak Syndrome
  • Longin domain
  • Lysosome-related organelles
  • Mon1
  • SNARE-like superfamily
  • Vesicle transport

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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