Document Detail


Protein interactions and disease phenotypes in the ABC transporter superfamily.
MedLine Citation:
PMID:  17990484     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ABC transporter proteins couple the energy of ATP binding and hydrolysis to substrate transport across a membrane. In humans, clinical studies have implicated mutations in 19 of the 48 known ABC transporters in diseases such as cystic fibrosis and adrenoleukodystrophy. Although divergent in sequence space, the overall topology of these proteins, consisting of two transmembrane domains and two ATP-binding cassettes, is likely to be conserved across diverse organisms. We examine known intra-transporter domain interfaces using crystallographic structures of isolated and complexed domains in ABC transporter proteins and find that the nucleotide binding domain interfaces are better conserved than interfaces at the transmembrane domains. We then apply this analysis to identify known disease-associated point and deletion mutants for which disruption of domain-domain interfaces might indicate the mechanism of disease. Finally, we suggest a possible interaction site based on conservation of sequence and disease-association of point mutants.
Authors:
Libusha Kelly; Rachel Karchin; Andrej Sali
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing     Volume:  -     ISSN:  2335-6936     ISO Abbreviation:  Pac Symp Biocomput     Publication Date:  2007  
Date Detail:
Created Date:  2007-11-09     Completed Date:  2007-12-20     Revised Date:  2013-02-20    
Medline Journal Info:
Nlm Unique ID:  9711271     Medline TA:  Pac Symp Biocomput     Country:  Singapore    
Other Details:
Languages:  eng     Pagination:  51-63     Citation Subset:  IM    
Affiliation:
Program in Biological and Medical Informatics, Department of Biopharmaceutical Sciences, University of California at San Francisco, CA 94158, USA. libusha@salilab.org
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / chemistry,  genetics*,  metabolism*
Binding Sites
Computational Biology
Computer Simulation
Conserved Sequence
Databases, Protein
Evolution, Molecular
Humans
Models, Molecular
Mutation*
Phenotype
Protein Interaction Mapping* / statistics & numerical data
Sequence Alignment
Grant Support
ID/Acronym/Agency:
F32 GM-072403-02/GM/NIGMS NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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