Abstract
The mechanism of cargo concentration into ER-derived vesicles involves interactions between the COPII vesicular coat complex and cargo transport signals--peptide sequences of 10-15 residues. The SNARE protein Sec22 contains a signal that binds the COPII subcomplex Sec23/24 and specifies its endoplasmic reticulum (ER) exit as an unassembled SNARE. The 200 kDa crystal structure of Sec22 bound to Sec23/24 reveals that the transport signal is a folded epitope rather than a conventional short peptide sequence. The NIE segment of the SNARE motif folds against the N-terminal longin domain, and this closed form of Sec22 binds at the Sec23/24 interface. Thus, COPII recognizes unassembled Sec22 via a folded epitope, whereas Sec22 assembly into SNARE complexes would mask the NIE segment. The concept of a conformational epitope as a transport signal suggests packaging mechanisms in which a coat is sensitive to the folded state of a cargo protein or the assembled state of a multiprotein complex.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Transport
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COP-Coated Vesicles / metabolism*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Computer Simulation
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Crystallography, X-Ray
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Endoplasmic Reticulum / metabolism
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Epitopes*
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Humans
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Models, Biological
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Molecular Sequence Data
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Multiprotein Complexes / chemistry
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Protein Binding
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Protein Conformation
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Protein Folding*
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Protein Sorting Signals*
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Protein Transport / physiology
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R-SNARE Proteins / chemistry
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R-SNARE Proteins / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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SNARE Proteins
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Vesicular Transport Proteins / chemistry
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Vesicular Transport Proteins / genetics
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Vesicular Transport Proteins / metabolism
Substances
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Carrier Proteins
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Epitopes
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Membrane Transport Proteins
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Multiprotein Complexes
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Protein Sorting Signals
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R-SNARE Proteins
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Recombinant Fusion Proteins
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SEC22A protein, human
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SEC23A protein, human
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SNARE Proteins
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Vesicular Transport Proteins
Associated data
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GENBANK/AAC39893
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GENBANK/AAS51681
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GENBANK/AAW26504
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GENBANK/ABF18345
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GENBANK/BAE61887
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GENBANK/CAA21224
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GENBANK/CAA92988
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GENBANK/CAB58402
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GENBANK/EAQ92206
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RefSeq/NP_006314
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RefSeq/NP_013370
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RefSeq/NP_014349
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RefSeq/NP_068817
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RefSeq/NP_172653
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RefSeq/NP_189008
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RefSeq/NP_610531
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RefSeq/NP_730979
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RefSeq/XP_394884
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RefSeq/XP_503201
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RefSeq/XP_646421
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RefSeq/XP_720881
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RefSeq/XP_784354
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RefSeq/XP_795453
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RefSeq/XP_823008
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RefSeq/XP_960888
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RefSeq/XP_961404
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RefSeq/XP_975087
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SWISSPROT/P15303
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SWISSPROT/Q15436
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SWISSPROT/Q15437