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PMID: 20052679 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Comparison of human solute carriers.

Protein science : a publication of the Protein Society ·Vol. 19 ·No. 3 ·2010-03-00 ·Pages 412-28

Schlessinger A, Matsson P, Shima JE, Pieper U, Yee SW, Kelly L, Apeltsin L, Stroud RM, Ferrin TE, Giacomini KM, Sali A

Abstract

Solute carriers are eukaryotic membrane proteins that control the uptake and efflux of solutes, including essential cellular compounds, environmental toxins, and therapeutic drugs. Solute carriers can share similar structural features despite weak sequence similarities. Identification of sequence relationships among solute carriers is needed to enhance our ability to model individual carriers and to elucidate the molecular mechanisms of their substrate specificity and transport. Here, we describe a comprehensive comparison of solute carriers. We link the proteins using sensitive profile-profile alignments and two classification approaches, including similarity networks. The clusters are analyzed in view of substrate type, transport mode, organism conservation, and tissue specificity. Solute carrier families with similar substrates generally cluster together, despite exhibiting relatively weak sequence similarities. In contrast, some families cluster together with no apparent reason, revealing unexplored relationships. We demonstrate computationally and experimentally the functional overlap between representative members of these families. Finally, we identify four putative solute carriers in the human genome. The solute carriers include a biomedically important group of membrane proteins that is diverse in sequence and structure. The proposed classification of solute carriers, combined with experiment, reveals new relationships among the individual families and identifies new solute carriers. The classification scheme will inform future attempts directed at modeling the structures of the solute carriers, a prerequisite for describing the substrate specificities of the individual families.

MeSH Terms
Amino Acid Sequence Conserved Sequence Drug Design Humans Membrane Transport Proteins/chemistry,classification Protein Conformation Sequence Alignment
Chemicals
Membrane Transport Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Schlessinger Avner
Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, California. schles@salilab.org
Matsson Pär
Shima James E
Pieper Ursula
Yee Sook Wah
Kelly Libusha
Apeltsin Leonard
Stroud Robert M
Ferrin Thomas E
Giacomini Kathleen M
Sali Andrej
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Article Info
Journal
Protein science : a publication of the Protein Society
Abbr.
Protein Sci
ISSN
1469-896X
DOI
10.1002/pro.320
Email
schles@salilab.org
Published
2010-03-00
Pages
412-28
Language
English
Region
United States
NLM ID
9211750
PMCID
PMC2866268
Subset
IM
Grants
NIGMS NIH HHS · U01 GM61390 · United States
NIGMS NIH HHS · R01 GM54762 · United States
NCRR NIH HHS · P41 RR01081 · United States
NIGMS NIH HHS · U54 GM074945 · United States
NCRR NIH HHS · P41 RR001081 · United States
NIGMS NIH HHS · U54 GM074929 · United States
External Links
PubMed source DOI: 10.1002/pro.320 PMC Full Text View journal details
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