AMINO-ACID-SEQUENCE ANALYSIS OF THE ANNEXIN SUPERGENE FAMILY OF PROTEINS
AMINO-ACID-SEQUENCE ANALYSIS OF THE ANNEXIN SUPERGENE FAMILY OF PROTEINS
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DOI：
10.1111/j.1432-1033.1991.tb16076.x
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发表时间：
1991-06-15
期刊：
影响因子：
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通讯作者：
CRUMPTON, MJ
中科院分区：
文献类型：
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作者：
BARTON, GJ;NEWMAN, RH;CRUMPTON, MJ
膜联蛋白是钙依赖性膜结合蛋白的广泛家族。没有共同的功能已被确定为家庭，直到最近，没有晶体学数据存在的膜联蛋白。在本文中，我们绘制了22个可用的膜联蛋白序列组成的88个相似的重复单元，并应用多序列比对，模式匹配，二级结构预测和保守性分析的分子的表征技术。分析清楚地表明，重复聚类成四个不同的家庭，最大的变化发生在重复3个单位。88个重复序列的多重比对显示在22个位置具有保守的理化性质的氨基酸，在所有重复序列中仅位置23处的Gly是绝对保守的。二级结构预测技术鉴定了每个重复单元中的5个保守螺旋，保守疏水性氨基酸的模式与预测螺旋a、c、d、e中对蛋白质核心的螺旋包装的一个面一致。阻碍B在所有重复序列中通常是疏水性的，但在位置31处包含重复序列特异性残基保守的显著模式，其中在重复序列4中具有Arg，在重复序列2中具有Glu，但在重复序列1和3中具有不保守的氨基酸。这表明重复序列2和4可能通过埋藏的盐桥相互作用。重复序列3的预测螺旋a和B之间的环显示出与重复序列1、2和4中的等同环不同的特征，表明该区域具有重要的结构和/或功能作用。这项研究没有令人信服的证据表明子宫珠蛋白和膜联蛋白具有相似的三级结构，或者子宫珠蛋白是原始单重复结构的衍生物，该结构经过复制形成了今天的膜联蛋白。在本文中进行的分析重新评估的附录中，在最近发表的X射线结构的人膜联蛋白V的结构证实了大多数的预测，并显示了权力的技术，用于确定的三级结构信息的氨基酸序列的对齐的蛋白质家族。
The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried salt-bridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.