Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus.
Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus.
复制标题
小家鼠激素原转化酶 1 前结构域的溶液结构。
DOI：
10.1016/s0022-2836(02)00543-0
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发表时间：
2002
影响因子：
5.6
通讯作者：
Orban,John
中科院分区：
文献类型：
--
作者：
Tangrea,MichaelA;Bryan,PhilipN;Sari,Nese;Orban,John
小鼠激素原转化酶（PC）1前结构域的溶液结构使用异相NMR光谱测定，并且是转化酶家族中任何结构域获得的第一个结构。NMR衍生结构的系综显示出由四链反平行β-折叠组成的有序核心，其中两个α-螺旋堆积在该折叠的一侧。序列同源性表明，其他真核生物PC前结构域将具有相同的整体折叠，并且形成PC 1的疏水核心的大多数残基在PC家族内是高度保守的。然而，一些核心残基被同源性预测为在其他PC前结构域中被极性氨基酸残基取代，这可能有助于解释它们的边缘稳定性。有趣的是，这里观察到的折叠拓扑结构也见于细菌枯草杆菌蛋白酶的前结构域，尽管几乎没有或没有序列同源性。原核和真核结构都具有聚集在其β-折叠的溶剂可及表面上的疏水残基，尽管单个残基类型不同。在细菌的情况下，该区域被掩埋在与催化结构域的结合界面处，并且在真核PC家族中，这些表面残基是保守的。因此，我们建议，在PC 1前域的疏水补丁参与其同源催化结构域以类似的方式看到的细菌系统的结合界面。PC 1前结构域的结构也揭示了潜在的机制，酸诱导的前和催化结构域之间的复合物的解离。
The solution structure of the mouse pro-hormone convertase (PC) 1 pro-domain was determined using heteronuclear NMR spectroscopy and is the first structure to be obtained for any of the domains in the convertase family. The ensemble of NMR-derived structures shows a well-ordered core consisting of a four-stranded antiparallel β-sheet with two α-helices packed against one side of this sheet. Sequence homology suggests that the other eukaryotic PC pro-domains will have the same overall fold and most of the residues forming the hydrophobic core of PC1 are highly conserved within the PC family. However, some of the core residues are predicted by homology to be replaced by polar amino acid residues in other PC pro-domains and this may help to explain their marginal stability. Interestingly, the folding topology observed here is also seen for the pro-domain of bacterial subtilisin despite little or no sequence homology. Both the prokaryotic and eukaryotic structures have hydrophobic residues clustered on the solvent-accessible surface of their β-sheets although the individual residue types differ. In the bacterial case this region is buried at the binding interface with the catalytic domain and, in the eukaryotic PC family, these surface residues are conserved. We therefore propose that the hydrophobic patch in the PC1 pro-domain is involved in the binding interface with its cognate catalytic domain in a similar manner to that seen for the bacterial system. The PC1 pro-domain structure also reveals potential mechanisms for the acid-induced dissociation of the complex between pro- and catalytic domains.