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Slc11a1 is an integral membrane protein with 12 putative TMDs and functions as a pH\u2010coupled divalent metal cation transporter. Glu139 of Slc11a1 is highly conserved within predicted TMD3 of the Slc11 protein family and function\u2010associated. Here, we provide the first direct experimental evidence for the structural features of two 24\u2010residue peptides corresponding to TMD3 of Slc11a1 and its E139A mutant in 60% HFIP\u2010d<jats:sub>2<\/jats:sub> aqueous solution using CD and NMR spectroscopies. Our study shows that the membrane\u2010spanning peptide folds as a typical amphipathic \u03b1\u2010helix structure from Ile5 to Met20 with hydrophilic residues Glu12 (Glu139 in Slc11a1) and Asp19 lying on the same side of the helix. The substitution of Glu139 by an alanine residue has little effect on the structure of the peptide, but increases hydrophobicity and facilitates self\u2010assembly of the peptide. Although the wildtype peptide is monomeric in HFIP aqueous solution, the E139A mutant forms a dimer. The increase in hydrophobicity of the membrane\u2010spanning peptide and\/or change in the interactions between transmembrane segments induced by E139A mutation may affect the metal ion transport of the protein. Copyright \u00a9 2010 European Peptide Society and John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/psc.1230","type":"journal-article","created":{"date-parts":[[2010,4,7]],"date-time":"2010-04-07T03:02:07Z","timestamp":1270609327000},"page":"249-255","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Study on structure and assembly of the third transmembrane domain of Slc11a1"],"prefix":"10.1002","volume":"16","author":[{"given":"Shuyan","family":"Xiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,4,6]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1139\/o06-193"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)00049-1"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.22.10089"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.09.006"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90135-D"},{"key":"e_1_2_6_7_2","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.4049\/jimmunol.157.8.3559","article-title":"Natural resistance to intracellular infections: Nramp1 encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nramp1D169) mouse strains","volume":"157","author":"Vidal SM","year":"1996","journal-title":"J. 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