Protein interactions and disease phenotypes in the ABC transporter superfamily

Libusha Kelly, Rachel Karchin, Andrej Sali

Research output: Chapter in Book/Report/Conference proceedingConference contribution

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Title of host publicationPacific Symposium on Biocomputing 2007, PSB 2007
Pages51-63
Number of pages13
StatePublished - 2007
Externally publishedYes
EventPacific Symposium on Biocomputing, PSB 2007 - Maui, HI, United States
Duration: Jan 3 2007Jan 7 2007

Publication series

NamePacific Symposium on Biocomputing 2007, PSB 2007

Other

OtherPacific Symposium on Biocomputing, PSB 2007
CountryUnited States
CityMaui, HI
Period1/3/071/7/07

ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Biomedical Engineering
  • Medicine(all)

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