Ancylostoma ceylanicum excretory-secretory protein 2 adopts a netrin-like fold and defines a novel family of nematode proteins.
Ancylostoma ceylanicum excretory-secretory protein 2 adopts a netrin-like fold and defines a novel family of nematode proteins.
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DOI：
10.1016/j.jmb.2011.02.033
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发表时间：
2011-04-22
影响因子：
5.6
通讯作者：
Modis Y
中科院分区：
文献类型：
--
作者：
Kucera K;Harrison LM;Cappello M;Modis Y
钩虫是人类的寄生虫，对全球健康造成破坏性影响，特别是在欠发达国家。锡兰钩虫感染人类和动物，使其成为研究疾病发病机制的有用模式生物。a.锡兰虫排泄-分泌蛋白2（AceES-2）是由成虫在肠附着部位分泌的高度免疫反应性分子，当作为粘膜疫苗施用以对抗钩虫贫血时具有部分保护性。在1.75 μ m分辨率下测定的AceES-2的晶体结构表明，AceES-2采用了与基质金属蛋白酶组织抑制剂（TIMP）以及补体因子C3和C5中发现的类似的网蛋白样折叠。然而，重组AceES-2不显著抑制十种最丰富的人基质金属蛋白酶或补体介导的细胞裂解。AceES-2表面的高酸性表明它可能作为细胞因子诱饵受体发挥作用。已被注释为TIMP或含netrin结构域的蛋白质的几种小线虫蛋白在AceES-2的netrin样折叠的结构重要区域中显示序列同源性。总之，我们的研究结果表明，AceES-2定义了一个新的家庭的线虫netrin样蛋白，这可能会起到调节宿主的免疫反应，钩虫和其他寄生虫。
Hookworms are human parasites that have devastating effects on global health, particularly in underdeveloped countries. Ancylostoma ceylanicum infects humans and animals, making it a useful model organism to study disease pathogenesis. A. ceylanicum excretory-secretory protein 2 (AceES-2), a highly immunoreactive molecule secreted by adult worms at the site of intestinal attachment, is partially protective when administered as a mucosal vaccine against hookworm anemia. The crystal structure of AceES-2 determined at 1.75 Å resolution shows that AceES-2 adopts a netrin-like fold similar to those found in tissue inhibitors of matrix metalloproteases (TIMPs), and in complement factors C3 and C5. However, recombinant AceES-2 does not significantly inhibit the ten most abundant human matrix metalloproteases, or complement-mediated cell lysis. The presence of a highly acidic surface on AceES-2 suggests that it may function as a cytokine decoy receptor. Several small nematode proteins that have been annotated as TIMPs or netrin domain-containing proteins display sequence homology in structurally important regions of AceES-2's netrin-like fold. Together, our results suggest that AceES-2 defines a novel family of nematode netrin-like proteins, which may function to modulate the host immune response to hookworm and other parasites.
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影响因子：
4
作者：
Fairfax KC;Vermeire JJ;Harrison LM;Bungiro RD;Grant W;Husain SZ;Cappello M
通讯作者：
Cappello M
影响因子：
1.5
作者：
Basavaraju, S;Zhan, B;Hotez, PJ
通讯作者：
Hotez, PJ
影响因子：
4.8
作者：
Cho, Yoonsang;Jones, Brian F.;Cappello, Michael
通讯作者：
Cappello, Michael
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
NTR模块：netrins、分泌型frizzled相关蛋白和I型胶原蛋白C蛋白酶增强蛋白的结构域与金属蛋白酶组织抑制剂同源
影响因子：
8
作者：
Bányai, L;Patthy, L
通讯作者：
Patthy, L