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

ABSTRACT: The appendage domain of the gammaCOP subunit of the COPI vesicle coat bears a striking structural resemblance to adaptin-family appendages despite limited primary sequence homology. Both the gammaCOP appendage domain and an equivalent region on betaCOP contain the FxxxW motif; the conservation of this motif suggested the existence of a functional appendage domain in betaCOP.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 betaCOP appendage and suggest that both COPI appendages perform a biologically active regulatory role with a structure related to adaptin-family appendage domains.

SUBMITTER: DeRegis CJ

PROVIDER: S-EPMC2262067 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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

DeRegis Carol J CJ Rahl Peter B PB Hoffman Gregory R GR Cerione Richard A RA Collins Ruth N RN

BMC cell biology 20080122

<h4>Background</h4>The appendage domain of the gammaCOP subunit of the COPI vesicle coat bears a striking structural resemblance to adaptin-family appendages despite limited primary sequence homology. Both the gammaCOP appendage domain and an equivalent region on betaCOP contain the FxxxW motif; the conservation of this motif suggested the existence of a functional appendage domain in betaCOP.<h4>Results</h4>Sequence comparisons in combination with structural prediction tools show that the fold ...[more]

PMID: 18211691

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Dataset Information

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

Publications

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

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