1. Academic Validation
  2. The transport signal on Sec22 for packaging into COPII-coated vesicles is a conformational epitope

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.
Joseph D Mancias 1 Jonathan Goldberg
Affiliations

Affiliation

  • 1 Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
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.

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