Structural basis of cargo membrane protein discrimination by the human COPII coat machinery Journal Article

Authors: Mancias, J. D.; Goldberg, J.
Article Title: Structural basis of cargo membrane protein discrimination by the human COPII coat machinery
Abstract: Genomic analysis shows that the increased complexity of trafficking pathways in mammalian cells involves an expansion of the number of SNARE, Rab and COP proteins. Thus, the human genome encodes four forms of Sec24, the cargo selection subunit of the COPII vesicular coat, and this is proposed to increase the range of cargo accommodated by human COPII-coated vesicles. In this study, we combined X-ray crystallographic and biochemical analysis with functional assays of cargo packaging into COPII vesicles to establish molecular mechanisms for cargo discrimination by human Sec24 subunits. A conserved IxM packaging signal binds in a surface groove of Sec24c and Sec24d, but the groove is occluded in the Sec24a and Sec24b subunits. Conversely, LxxLE class transport signals and the DxE signal of VSV glycoprotein are selectively bound by Sec24a and Sec24b subunits. A comparative analysis of crystal structures of the four human Sec24 isoforms establishes the structural determinants for discrimination among these transport signals, and provides a framework to understand how an expansion of coat subunits extends the range of cargo proteins packaged into COPII-coated vesicles. ©2008 European Molecular Biology Organization.
Keywords: signal transduction; controlled study; unclassified drug; human cell; nonhuman; comparative study; protein analysis; animal cell; mammalia; animals; embryo; molecular dynamics; cell line; protein binding; membrane proteins; protein interaction; endoplasmic reticulum; amino acid sequence; conserved sequence; molecular sequence data; molecular recognition; nucleotide sequence; membrane protein; protein transport; crystal structure; models, molecular; crystallography, x-ray; binding sites; protein subunit; protein structure; x ray crystallography; biochemistry; protein determination; protein structure, secondary; glycoprotein; protein isoforms; cricetinae; vesicular transport proteins; vesicular transport; coat protein complex ii; cop-coated vesicles; surface property; vesicular stomatitis virus; copii coat; transport signal; membrin; syntaxin 5; transport vesicle; protein sorting signals; qa-snare proteins; qb-snare proteins
Journal Title: EMBO Journal
Volume: 27
Issue: 21
ISSN: 0261-4189
Publisher: Wiley Blackwell  
Date Published: 2008-11-05
Start Page: 2918
End Page: 2928
Language: English
DOI: 10.1038/emboj.2008.208
PUBMED: 18843296
PROVIDER: scopus
PMCID: PMC2580787
Notes: --- - "Cited By (since 1996): 27" - "Export Date: 17 November 2011" - "CODEN: EMJOD" - "Molecular Sequence Numbers: GENBANK: AAH35761, AAH54249, CAB58402, CAJ83820, NP_003155, NP_004278, NP_004913, NP_013126, NP_013179, NP_014349, NP_113872, NP_502178, NP_505968, NP_599132, Q08851, XP_392952, XP_449343, XP_638899, XP_642481, XP_958077;" - "Source: Scopus"
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