Lack of involvement of strand s1'A of the viral serpin CrmA in anti-apoptotic or caspase-inhibitory functions.
Lack of involvement of strand s1'A of the viral serpin CrmA in anti-apoptotic or caspase-inhibitory functions.
复制标题
病毒丝氨酸蛋白酶抑制剂 CrmA 的 s1A 链缺乏抗凋亡或半胱天冬酶抑制功能。
DOI：
10.1016/j.abb.2005.05.018
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Gettins,PeterGW
中科院分区：
文献类型：
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作者：
Simonovic,Miljan;Denault,Jean-Bernard;Salvesen,GuyS;Volz,Karl;Gettins,PeterGW
CrmA is a cowpox virus serpin required for full host infectivity and virulence. Residues 51–56 (DKNKDD), the only region that differs significantly from related viral serpins, were investigated for functional importance. A 1.6Å X-ray structure reported here showed that this region can adopt either structured or unstructured conformations. Three variants were expressed, one with the region 51–56 deleted, one substituted by alanines, and one in which this region was replaced by the sequence encoded in smallpox virus. NMR showed that the region is an exposed, flexible loop that can be deleted without perturbing the serpin. The region is also very susceptible to proteolysis. Significantly, inhibition of caspases 1 and 8 was unaffected by the mutations, and each of the variants was as effective as wild-type CrmA in promoting survival from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Thus, although the 51–56 region of CrmA is unique, and is exposed and highly susceptible to proteolysis, any in vivo role must involve a function other than proteinase inhibition or cell sparing.
