Department für biowissenschaftliche Grundlagen, Lehrstuhl für Genomorientierte Bioinformatik, Technische Universität München, Freising, Germany.
Proteins. 2011 Aug;79(8):2418-27. doi: 10.1002/prot.23063. Epub 2011 Jun 1.
SNARE proteins and fusogenic viral membrane proteins represent the major classes of integral membrane proteins that mediate fusion of eukaryotic lipid bilayers. Although both classes have different primary structures, they share a number of basic architectural features. There is ample evidence that the fusogenic function of representative fusion proteins is influenced by the primary structure of the single transmembrane domain (TMD) and the region linking it to the soluble assembly domains. Here, we used comprehensive non-redundant datasets to examine potential over- and underrepresentation of amino acid types in the TMDs and flanking regions relative to control proteins that share similar biosynthetic origins. Our results reveal conserved overall and/or site-specific enrichment of β-branched residues and Gly within the TMDs, underrepresentation of Gly and Pro in regions flanking the TMD N-terminus, and overrepresentation of the same residue types in C-terminal flanks of SNAREs and viral fusion proteins. Furthermore, the basic Lys and Arg are enriched within SNARE N-terminal flanking regions. These results suggest evolutionary conservation of key structural features of fusion proteins and are discussed in light of experimental findings that link these features to the fusogenic function of these proteins.
SNARE 蛋白和融合病毒膜蛋白代表了主要的整合膜蛋白类别，它们介导真核脂双层的融合。尽管这两类蛋白具有不同的一级结构，但它们具有许多基本的结构特征。有充分的证据表明，代表性融合蛋白的融合功能受单一跨膜域 (TMD) 的一级结构和将其连接到可溶性组装域的区域的影响。在这里，我们使用全面的非冗余数据集，相对于具有相似生物合成起源的对照蛋白，检查 TMD 和侧翼区域中氨基酸类型的过度和不足表达的情况。我们的结果揭示了 TMD 中β支化残基和甘氨酸的总体和/或特定位点的保守富集，TMD N 端侧翼区域中甘氨酸和脯氨酸的不足表达，以及 SNARE 和病毒融合蛋白 C 端侧翼相同残基类型的过度表达。此外，碱性赖氨酸和精氨酸在 SNARE N 端侧翼区域中富集。这些结果表明融合蛋白的关键结构特征在进化上是保守的，并结合这些特征与这些蛋白的融合功能的实验发现进行了讨论。
