古菌 Na+/H+ 反向转运蛋白 NhaP1 的结构及其跨膜螺旋 1 的功能作用。
Structure of the archaeal Na+/H+ antiporter NhaP1 and functional role of transmembrane helix 1.
机构信息
Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
出版信息
EMBO J. 2011 Jan 19;30(2):439-49. doi: 10.1038/emboj.2010.321. Epub 2010 Dec 10.
Abstract
We have determined the structure of the archaeal sodium/proton antiporter NhaP1 at 7 Å resolution by electron crystallography of 2D crystals. NhaP1 is a dimer in the membrane, with 13 membrane-spanning α-helices per protomer, whereas the distantly related bacterial NhaA has 12. Dimer contacts in the two antiporters are very different, but the structure of a six-helix bundle at the tip of the protomer is conserved. The six-helix bundle of NhaA contains two partially unwound α-helices thought to harbour the ion-translocation site, which is thus similar in NhaP1. A model of NhaP1 based on detailed sequence comparison and the NhaA structure was fitted to the 7 Å map. The additional N-terminal helix 1 of NhaP1, which appears to be an uncleaved signal sequence, is located near the dimer interface. Similar sequences are present in many eukaryotic homologues of NhaP1, including NHE1. Although fully folded and able to dimerize, NhaP1 constructs without helix 1 are inactive. Possible reasons are investigated and discussed.
摘要
我们通过二维晶体的电子晶体学确定了古细菌钠/质子反向转运蛋白 NhaP1 的 7 Å 分辨率结构。NhaP1 在膜中是二聚体，每个单体有 13 个跨膜α螺旋，而远亲的细菌 NhaA 有 12 个。两种反向转运蛋白的二聚体接触非常不同，但在单体顶端的六螺旋束的结构是保守的。NhaA 的六螺旋束包含两个部分展开的α螺旋，据认为它们包含离子转运位点，因此在 NhaP1 中也是如此。基于详细的序列比较和 NhaA 结构的 NhaP1 模型被拟合到 7 Å 图谱中。NhaP1 的额外 N 端螺旋 1 似乎是未切割的信号序列，位于二聚体界面附近。许多 NhaP1 的真核同源物中都存在类似的序列，包括 NHE1。尽管完全折叠并能够二聚化，但没有螺旋 1 的 NhaP1 构建体是无活性的。我们探讨并讨论了可能的原因。
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