Pathway of binding of the intrinsically disordered mitochondrial inhibitor protein to F1-ATPase
Pathway of binding of the intrinsically disordered mitochondrial inhibitor protein to F1-ATPase
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DOI：
10.1073/pnas.1411560111
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发表时间：
2014-08-05
影响因子：
11.1
通讯作者：
Walker, John E.
中科院分区：
文献类型：
--
作者：
Bason, John V.;Montgomery, Martin G.;Walker, John E.
线粒体中ATP合酶对ATP的水解被一种称为IF 1的蛋白质抑制。牛IF 1由84个氨基酸组成，其N-末端抑制区本质上是无序的。在被IF 1的残基1-60抑制的牛F-1-ATP酶的已知结构中，残基1-50的抑制区域主要是α-螺旋的并且深埋在α（DP）β（DP）-催化界面处，在那里它与F-1-ATP酶的9个亚基中的5个形成广泛的相互作用，但主要与β（DP）-亚基形成广泛的相互作用。如本文所述，基于在IF 1的残基1-60和具有突变K39 A的IF 1的变体的大摩尔过量存在下形成的抑制复合物的两种结构，似乎本质无序的抑制区首先与α（E）β（E）-催化界面相互作用，这是三个催化界面中最开放的，其中与酶的可利用的相互作用允许其从残基31-49形成α-螺旋。然后，响应于ATP分子的水解和相关的界面部分闭合为α（TP）β（TP）状态，IF 1的折叠α-螺旋区域的范围增加到残基23-50，因为与酶的更多相互作用变得可能。最后，响应于第二个ATP分子的水解和伴随的γ亚基的120度旋转，界面进一步接近α（DP）β（DP）状态，允许酶和IF 1之间形成更多的相互作用。IF 1的结构现在延伸到它的最大折叠状态，发现在以前观察到的抑制复合物。
The hydrolysis of ATP by the ATP synthase in mitochondria is inhibited by a protein called IF1. Bovine IF1 has 84 amino acids, and its N-terminal inhibitory region is intrinsically disordered. In a known structure of bovine F-1-ATPase inhibited with residues 1-60 of IF1, the inhibitory region from residues 1-50 is mainly alpha-helical and buried deeply at the alpha(DP)beta(DP)-catalytic interface, where it forms extensive interactions with five of the nine subunits of F-1-ATPase but mainly with the beta(DP)-subunit. As described here, on the basis of two structures of inhibited complexes formed in the presence of large molar excesses of residues 1-60 of IF1 and of a version of IF1 with the mutation K39A, it appears that the intrinsically disordered inhibitory region interacts first with the alpha(E)beta(E)-catalytic interface, the most open of the three catalytic interfaces, where the available interactions with the enzyme allow it to form an alpha-helix from residues 31-49. Then, in response to the hydrolysis of an ATP molecule and the associated partial closure of the interface to the alpha(TP)beta(TP) state, the extent of the folded alpha-helical region of IF1 increases to residues 23-50 as more interactions with the enzyme become possible. Finally, in response to the hydrolysis of a second ATP molecule and a concomitant 120 degrees rotation of the gamma-subunit, the interface closes further to the alpha(DP)beta(DP)-state, allowing more interactions to form between the enzyme and IF1. The structure of IF1 now extends to its maximally folded state found in the previously observed inhibited complex.