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Open Access Research article

Mutational analysis of βCOP (Sec26p) identifies an appendage domain critical for function

Carol J DeRegis1, Peter B Rahl2, Gregory R Hoffman3, Richard A Cerione45 and Ruth N Collins46*

Author affiliations

1 Graduate Program in Comparative Biomedical Sciences, Cornell University, Ithaca NY 14853, USA

2 Graduate Program in Pharmacology, Cornell University, Ithaca, NY 14853, USA

3 Graduate Program in Biophysics, Cornell University, Ithaca, NY 14853, USA

4 Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA

5 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA

6 Department of Molecular Medicine, Cornell University, C4-109 Veterinary Medical Center, Ithaca, NY 14853, USA

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Citation and License

BMC Cell Biology 2008, 9:3  doi:10.1186/1471-2121-9-3

Published: 22 January 2008



The appendage domain of the γCOP subunit of the COPI vesicle coat bears a striking structural resemblance to adaptin-family appendages despite limited primary sequence homology. Both the γCOP appendage domain and an equivalent region on βCOP contain the FxxxW motif; the conservation of this motif suggested the existence of a functional appendage domain in βCOP.


Sequence comparisons in combination with structural prediction tools show that the fold of the COOH-terminus of Sec26p is strongly predicted to closely mimic that of adaptin-family appendages. Deletion of the appendage domain of Sec26p results in inviability in yeast, over-expression of the deletion construct is dominant negative and mutagenesis of this region identifies residues critical for function. The ArfGAP Glo3p was identified via suppression screening as a potential downstream modulator of Sec26p in a manner that is independent of the GAP activity of Glo3p but requires the presence of the COOH-terminal ISS motifs.


Together, these results indicate an essential function for the predicted βCOP appendage and suggest that both COPI appendages perform a biologically active regulatory role with a structure related to adaptin-family appendage domains.