3EG9

Crystal structure of the mammalian COPII-coat protein Sec23/24 bound to the transport signal sequence of membrin

Summary for 3EG9

• Entry DOI: 10.2210/pdb3eg9/pdb
• Related: 3EFO 3EGD
• Descriptor: Protein transport protein Sec23A, SEC24 related gene family, member D, peptide, ... (5 entities in total)
• Functional Keywords: copii coat, vesicle transport, transport signal sequence, disease mutation, endoplasmic reticulum, er-golgi transport, golgi apparatus, membrane, protein transport, transport
• Biological source: Homo sapiens (Human); More
• Cellular location: Smooth endoplasmic reticulum membrane; Peripheral membrane protein: Q15436
• Total number of polymer chains: 3
• Total formula weight: 173720.94

Authors

Goldberg, J.,Mancias, J.D. (deposition date: 2008-09-10, release date: 2008-10-21, Last modification date: 2023-08-30)

Primary citation

Mancias, J.D.,Goldberg, J.
Structural basis of cargo membrane protein discrimination by the human COPII coat machinery.
Embo J., 27:2918-2928, 2008

PubMed 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.

PubMed: 18843296
DOI: 10.1038/emboj.2008.208

Experimental method

X-RAY DIFFRACTION (3 Å)