Crystal structure of a hedgehog autoprocessing domain: Homology between hedgehog and self-splicing proteins
Crystal structure of a hedgehog autoprocessing domain: Homology between hedgehog and self-splicing proteins
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DOI：
10.1016/s0092-8674(01)80011-8
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发表时间：
1997-10-03
期刊：
影响因子：
64.5
通讯作者：
Leahy, DJ
中科院分区：
文献类型：
--
作者：
Hall, TMT;Porter, JA;Leahy, DJ
果蝇Hedgehog蛋白（Hh-C）的25 kDa羧基末端结构域具有自加工活性，可导致全长Hedgehog蛋白的分子内裂解，并将胆固醇部分共价连接到新产生的氨基末端片段上。我们已经确定了一个17 kDa的片段的Hh-C（Hh-C-17）在启动自动加工的活性，并在这里报告其晶体结构。Hh-C-17结构包括两个同源亚结构域，它们似乎是由原始基因的串联复制产生的。Hh-C-17活性位点中的残基已经被鉴定，并且它们在Hedgehog自动加工中的作用通过定点诱变来探测。Hh-C-17和内含肽的自剪接区域之间的序列、结构和反应机制方面是保守的，允许重建Hh-C和内含肽的合理进化历史。
The similar to 25 kDa carboxy-terminal domain of Drosophila Hedgehog protein (Hh-C) possesses an autoprocessing activity that results in an intramolecular cleavage of full-length Hedgehog protein and covalent attachment of a cholesterol moiety to the newly generated amino-terminal fragment. We have identified a 17 kDa fragment of Hh-C (Hh-C-17) active in the initiation of autoprocessing and report here its crystal structure. The Hh-C-17 structure comprises two homologous subdomains that appear to have arisen from tandem duplication of a primordial gene. Residues in the Hh-C-17 active site have been identified, and their role in Hedgehog autoprocessing probed by site-directed mutagenesis. Aspects of sequence, structure, and reaction mechanism are conserved between Hh-C-17 and the self-splicing regions of inteins, permitting reconstruction of a plausible evolutionary history of Hh-C and the inteins.