Lundin Carolina, Kim Hyun, Nilsson IngMarie, White Stephen H, von Heijne Gunnar
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15702-7. doi: 10.1073/pnas.0804842105. Epub 2008 Oct 7.
Transmembrane alpha-helices in integral membrane proteins can have two orientations in the membrane: N(in)-C(out) or N(out)-C(in). Previous studies of model N(out)-C(in) transmembrane segment have led to a detailed, quantitative picture of the "molecular code" that relates amino acid sequence to membrane insertion efficiency in vivo [Hessa T, et al. (2007) Molecular code for transmembrane helix recognition by the Sec61 translocon. Nature 450:1026-1030], but whether the same code applies also to N(in)-C(out) transmembrane helices is unknown. Here, we show that the contributions of individual amino acids to the overall efficiency of membrane insertion are similar for the two kinds of helices and that the threshold hydrophobicity for membrane insertion can be up to approximately 1 kcal/mol lower for N(in)-C(out) compared with N(out)-C(in) transmembrane helices, depending on the neighboring helices.
整合膜蛋白中的跨膜α螺旋在膜中可有两种取向：N端在内-C端在外或N端在外-C端在内。先前对模型N端在外-C端在内跨膜片段的研究已得出了一个详细的、定量的“分子密码”图景，该密码将氨基酸序列与体内膜插入效率联系起来[赫萨T等人（2007年）。Sec61转运体识别跨膜螺旋的分子密码。《自然》450:1026 - 1030]，但同样的密码是否也适用于N端在内-C端在外的跨膜螺旋尚不清楚。在此，我们表明，对于这两种螺旋，单个氨基酸对膜插入总体效率的贡献是相似的，并且与N端在外-C端在内的跨膜螺旋相比，N端在内-C端在外跨膜螺旋的膜插入阈值疏水性可低约1千卡/摩尔，这取决于相邻螺旋。
