A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization
A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization
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DOI：
10.1038/nsmb1275
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发表时间：
2007-08-01
影响因子：
16.8
通讯作者：
Skach, William R.
中科院分区：
文献类型：
--
作者：
Buck, Teresa M.;Wagner, Justin;Skach, William R.
水通道蛋白（AQP）在内质网中的折叠以两种不同的膜插入途径为特征，这两种途径是由第二跨膜段内的不同残基产生的。我们现在发现在AQP1中，这些残基（Asn49和Lys51）在TM5的C端与Asp185相互作用，形成一个极性的四级结构基序，影响折叠的多个阶段。Asn49和Asp185形成分子内氢键，这是正确的螺旋填充、单体形成和功能所必需的。相反，Lys51与相邻单体上的Asp185相互作用以稳定AQP1四聚体。虽然这些残基是AQP1独有的，但它们具有高度保守的结构，其功能特性可以转移给其他家族成员。这些发现提示了一种普遍的机制，通过这种机制，膜蛋白的进化分化可以通过不同的折叠途径赋予新的功能特性，从而产生共同的最终结构。
Aquaporin (AQP) folding in the endoplasmic reticulum is characterized by two distinct pathways of membrane insertion that arise from divergent residues within the second transmembrane segment. We now show that in AQP1 these residues (Asn49 and Lys51) interact with Asp185 at the C terminus of TM5 to form a polar, quaternary structural motif that influences multiple stages of folding. Asn49 and Asp185 form an intramolecular hydrogen bond needed for proper helical packing, monomer formation and function. In contrast, Lys51 interacts with Asp185 on an adjacent monomer to stabilize the AQP1 tetramer. Although these residues are unique to AQP1, they share a highly conserved architecture whose functional properties can be transferred to other family members. These findings suggest a general mechanism by which evolutionary divergence of membrane proteins can confer new functional properties via alternative folding pathways that give rise to a common final structure.