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The structure and assembly model of the third transmembrane domain of Slc11a1 in SDS micelles revealed by NMR study of the Leu-substituted peptide

Authors


Fei Li, State Key Laboratory of Supramolecular Structure and Materials, Jilin University, 2699 Qianjin Avenue, Changchun 130012, China. E-mail: feili@jlu.edu.cn

Abstract

Slc11a1 is an integral membrane protein with 12 putative transmembrane domains (TMDs) and functions as a pH-coupled divalent metal cation transporter. The conservation of three negatively charged residues in the TMD3 of Slc11 protein family implies the important role of this domain in the function of the proteins. However, aggregation of the transmembrane peptide in micelles prevents structural study of the peptide in these membrane-mimetic environments by NMR spectroscopy. Here, we characterized the structure, position, and assembly model of Slc11a1-TMD3 (Lys128-Ile151) in SDS micelles by the NMR study of its Leu-substituted peptide. It was found that the two-site substitutions of Ala for Leu residues at positions 136 and 140 of TMD3 disrupt the aggregation without altering the secondary structure of the peptide. The Leu-substituted peptide folds as an α-helix spanning from Leu133 to Gly144 and embedded in the micelles. A Leu zipper is suggested to account for the self-assembly of the wild-type peptide in SDS micelles. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

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