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Toward a Topological Model of the NCX1 Exchanger
Author(s) -
NICOLL DEBORA A.,
OTTOLIA MICHELA,
PHILIPSON KENNETH D.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04709.x
Subject(s) - transmembrane protein , transmembrane domain , amino acid , mutagenesis , peptide sequence , sodium calcium exchanger , chemistry , cysteine , biophysics , mutant , biochemistry , intracellular , biology , gene , enzyme , receptor
A bstract : The Na + /Ca 2+ exchanger (NCX1) catalyzes the counter‐transport of sodium and calcium ions. Understanding how this is accomplished requires knowledge of the structure of NCX1 and identifying amino acid residues involved in binding and transport of ions. The amino acid sequence of NCX1 has been known for more than a decade. Based on hydropathy analysis, NCX1 was modeled to contain 12 transmembrane segments. In this model, the α‐repeat regions, which are the result of a gene duplication event (see below), are oriented on the extracellular face of NCX1. In the years since NCX1 was sequenced, a considerable amount of effort has gone into testing the initial 12‐transmembrane‐segment model. Immunologic and protein‐processing studies as well as functional analyses of mutants have determined the location of the amino and carboxy termini and several intracellular regions. However, disulfide bond analysis and cysteine mutagenesis coupled with accessibility studies indicate that the structure of NCX1 diverges from a simple membrane protein consisting only of transmembrane α‐helical segments. These recent data support a model containing 9 transmembrane α‐helices with the α‐repeat regions forming nonhelical re‐entrant loops. A bacterial protein containing a pair of α‐repeat regions but of unknown function has also been shown to have oppositely oriented α‐repeats.