The transport signal on Sec22 for packaging into COPII-coated vesicles is a conformational epitope

Mol Cell. 2007 May 11;26(3):403-14. doi: 10.1016/j.molcel.2007.03.017.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • COP-Coated Vesicles / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Computer Simulation
  • Crystallography, X-Ray
  • Endoplasmic Reticulum / metabolism
  • Epitopes*
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Protein Binding
  • Protein Conformation
  • Protein Folding*
  • Protein Sorting Signals*
  • Protein Transport / physiology
  • R-SNARE Proteins / chemistry
  • R-SNARE Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • SNARE Proteins
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • Carrier Proteins
  • Epitopes
  • Membrane Transport Proteins
  • Multiprotein Complexes
  • Protein Sorting Signals
  • R-SNARE Proteins
  • Recombinant Fusion Proteins
  • SEC22A protein, human
  • SEC23A protein, human
  • SNARE Proteins
  • Vesicular Transport Proteins

Associated data

  • GENBANK/AAC39893
  • GENBANK/AAS51681
  • GENBANK/AAW26504
  • GENBANK/ABF18345
  • GENBANK/BAE61887
  • GENBANK/CAA21224
  • GENBANK/CAA92988
  • GENBANK/CAB58402
  • GENBANK/EAQ92206
  • RefSeq/NP_006314
  • RefSeq/NP_013370
  • RefSeq/NP_014349
  • RefSeq/NP_068817
  • RefSeq/NP_172653
  • RefSeq/NP_189008
  • RefSeq/NP_610531
  • RefSeq/NP_730979
  • RefSeq/XP_394884
  • RefSeq/XP_503201
  • RefSeq/XP_646421
  • RefSeq/XP_720881
  • RefSeq/XP_784354
  • RefSeq/XP_795453
  • RefSeq/XP_823008
  • RefSeq/XP_960888
  • RefSeq/XP_961404
  • RefSeq/XP_975087
  • SWISSPROT/P15303
  • SWISSPROT/Q15436
  • SWISSPROT/Q15437