Hessa Tara, Kim Hyun, Bihlmaier Karl, Lundin Carolina, Boekel Jorrit, Andersson Helena, Nilsson Ingmarie, White Stephen H, von Heijne Gunnar
Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Nature. 2005 Jan 27;433(7024):377-81. doi: 10.1038/nature03216.
Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein-lipid interactions are critical during translocon-mediated membrane insertion.
膜蛋白插入靶膜依赖于复杂的转运机制。尽管长期以来人们都知道跨膜螺旋中大量的非极性残基是膜插入的主要标准，但尚未确定跨膜螺旋的特定序列编码。通过用大量设计的多肽片段挑战内质网Sec61转运体，我们确定了该编码的基本特征，包括一个“生物学”疏水性标度。我们发现膜插入强烈依赖于跨膜段内极性残基的位置，这为从氨基酸序列预测跨膜螺旋的问题增添了新的维度。我们的结果表明，在转运体介导的膜插入过程中，直接的蛋白质-脂质相互作用至关重要。
