Structural Basis of Cargo Membrane Protein Discrimination by the Human COPll Coat Machinery

Journal Article · Tue Jan 01 04:00:00 EST 2008 · EMBO Journal

DOI:https://doi.org/10.1038/emboj.2008.208· OSTI ID:980509

Mancias, J; Goldberg, J

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 980509
• Report Number(s): BNL--93427-2010-JA
• Journal Information: EMBO Journal, Journal Name: EMBO Journal Vol. 27; ISSN EMJODG; ISSN 0261-4189
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CARGO
CRYSTAL STRUCTURE
EXPANSION
FUNCTIONALS
GLYCOPROTEINS
HUMAN POPULATIONS
MACHINERY
MEMBRANE PROTEINS
PACKAGING
PROTEINS
RANGE
SIGNALS
SURFACES
TRANSPORT
national synchrotron light source