RGD Reference Report - Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease. - Rat Genome Database

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Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease.

Authors: Rak, A  Pylypenko, O  Niculae, A  Pyatkov, K  Goody, RS  Alexandrov, K 
Citation: Rak A, etal., Cell. 2004 Jun 11;117(6):749-60.
RGD ID: 8553294
Pubmed: (View Article at PubMed) PMID:15186776
DOI: Full-text: DOI:10.1016/j.cell.2004.05.017

Members of the RabGDI/REP family serve as multifunctional regulators of the Rab family of GTP binding proteins. Mutations in members of this family, such as REP-1, lead to abnormalities, including progressive retinal degradation (choroideremia) in humans. The crystal structures of the REP-1 protein in complex with monoprenylated or C-terminally truncated Rab7 proteins revealed that Rab7 interacts with the Rab binding platform of REP-1 via an extended interface involving the Switch 1 and 2 regions. The C terminus of the REP-1 molecule functions as a mobile lid covering a conserved hydrophobic patch on the surface of REP-1 that in the complex coordinates the C terminus of Rab proteins. Using semisynthetic fluorescent Rab27A, we demonstrate that although Rab27A can be prenylated by REP-2, this reaction can be effectively inhibited by other Rab proteins, providing a possible explanation for the accumulation of unprenylated Rab27A in choroideremia.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Chm  (CHM Rab escort protein)
Rab7a  (RAB7A, member RAS oncogene family)


Additional Information