Comparison of H+-ATPase and Ca2+-ATPase suggests that a large conformational change initiates P-type ion pump reaction cycles.
Comparison of H+-ATPase and Ca2+-ATPase suggests that a large conformational change initiates P-type ion pump reaction cycles.
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H-ATP酶和Ca2-ATP酶的比较表明，大的构象变化启动了P型离子泵反应循环。
DOI：
10.1016/s0960-9822(99)80307-8
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Kühlbrandt,W
中科院分区：
文献类型：
--
作者：
Stokes,DL;Auer,M;Zhang,P;Kühlbrandt,W
背景：兔肌浆网Ca ~（2+）-ATP酶和粗糙脉孢菌H ~+-ATP酶的结构在8 μ m分辨率下已被解析。这些阳离子泵是P型ATP酶家族的两个远亲成员，它们被认为使用类似的机制来产生跨各种细胞膜的ATP依赖性离子梯度。我们已经进行了详细的比较，以描述它们的相似性和差异，因为他们承担他们的主动transport.Results的机制：我们的第一个重要发现是，10个跨膜螺旋的安排是非常相似的两个分子。这种结构上的同源性有力地支持了这样一种观点，即这些泵使用相同的基本机制来输送它们各自的离子。尽管在跨膜区域的这种相似性，两个分子的细胞质区域是非常不同的，无论是在他们的处置相对于膜和并列的各种subdomains.Conclusions：结晶条件的基础上，我们提出，这两个晶体结构代表不同的中间体在运输周期中，区分是否阳离子结合到他们的运输网站。此外，我们提出相应的构象变化（E2到E1）有两个组成部分：第一个是相对于跨膜结构域的主细胞质质量的20°的倾斜;第二个是结构域的重排，包括分子的细胞质部分。因此，我们提出了一个粗略的模型，这一重要的构象变化，中继跨膜结构域内的核苷酸结合位点的阳离子结合的影响，从而启动运输周期。
Background:Structures have recently been solved at 8 å resolution for both Ca2+-ATPase from rabbit sarcoplasmic reticulum and H+-ATPase fromNeurospora crassa. These cation pumps are two distantly related members of the family of P-type ATPases, which are thought to use similar mechanisms to generate ATP-dependent ion gradients across a variety of cellular membranes. We have undertaken a detailed comparison of the two structures in order to describe their similarities and differences as they bear on their mechanism of active transport.Results:Our first important finding was that the arrangement of 10 transmembrane helices was remarkably similar in the two molecules. This structural homology strongly supports the notion that these pumps use the same basic mechanism to transport their respective ions. Despite this similarity in the membrane-spanning region, the cytoplasmic regions of the two molecules were very different, both in their disposition relative to the membrane and in the juxtaposition of their various subdomains.Conclusions:On the basis of the crystallization conditions, we propose that these two crystal structures represent different intermediates in the transport cycle, distinguished by whether cations are bound to their transport sites. Furthermore, we propose that the corresponding conformational change (E2to E1) has two components: the first is an inclination of the main cytoplasmic mass by 20° relative to the membrane-spanning domain; the second is a rearrangement of the domains comprising the cytoplasmic part of the molecules. Accordingly, we present a rough model for this important conformational change, which relays the effects of cation binding within the membrane-spanning domain to the nucleotide-binding site, thus initiating the transport cycle.