Dimerization of Plasmodium vivax DBP is induced upon receptor binding and drives recognition of DARC.
Dimerization of Plasmodium vivax DBP is induced upon receptor binding and drives recognition of DARC.
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DOI：
10.1038/nsmb.2088
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发表时间：
2011-07-10
影响因子：
16.8
通讯作者：
Tolia, Niraj H.
中科院分区：
文献类型：
--
作者：
Batchelor, Joseph D.;Zahm, Jacob A.;Tolia, Niraj H.
间日疟原虫和诺氏疟原虫在侵入过程中依赖于与红细胞上的Duffy抗原/趋化因子受体接合的Duffy结合蛋白DBL结构域（RII-PvDBP或RII-PkDBP）。这种关键相互作用的抑制为寄生虫控制提供了极好的机会。疟原虫配体是否与受体结合为单体或二聚体存在竞争模型，其分辨率对寄生虫生物学和控制具有深远意义。我们报告了RII-PvDBP的晶体学、溶液和功能研究，表明二聚化是受体接合所需并由受体接合驱动的。这项工作为先前的研究提供了一个统一的框架，并解释了自然获得的阻断抗体的作用和免疫逃避的机制。我们发现二聚化在DBL结构域受体参与中是保守的，并提出受体介导的配体二聚化驱动受体亲和力和特异性。由于二聚化在信号传导中普遍存在，我们的研究提出了诱导二聚化激活入侵途径的可能性。
Plasmodium vivax and Plasmodium knowlesi depend on the Duffy-Binding Protein DBL domain (RII-PvDBP or RII-PkDBP) engaging Duffy Antigen/Receptor for Chemokines on red blood cells during invasion. Inhibition of this key interaction provides an excellent opportunity for parasite control. There are competing models for whether Plasmodium ligands engage receptors as monomers or dimers, resolution of which has profound implications for parasite biology and control. We report crystallographic, solution and functional studies of RII-PvDBP, showing dimerization is required for and driven by receptor engagement. This work provides a unifying framework for prior studies and accounts for the action of naturally-acquired blocking-antibodies and the mechanism of immune evasion. We show dimerization is conserved in DBL-domain receptor-engagement, and propose receptor-mediated ligand-dimerization drives receptor affinity and specificity. Since dimerization is prevalent in signaling, our studies raise the possibility that induced dimerization activates pathways for invasion.
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影响因子：
1.5
作者：
Jia, XL;Adams, JH;King, CL
通讯作者：
King, CL
影响因子：
64.8
作者：
Carlton, Jane M.;Adams, John H.;Silva, Joana C.;Bidwell, Shelby L.;Lorenzi, Hernan;Caler, Elisabet;Crabtree, Jonathan;Angiuoli, Samuel V.;Merino, Emilio F.;Amedeo, Paolo;Cheng, Qin;Coulson, Richard M. R.;Crabb, Brendan S.;del Portillo, Hernando A.;Essien, Kobby;Feldblyum, Tamara V.;Fernandez-Becerra, Carmen;Gilson, Paul R.;Gueye, Amy H.;Guo, Xiang;Kang'a, Simon;Kooij, Taco W. A.;Korsinczky, Michael;Meyer, Esmeralda V. -S.;Nene, Vish;Paulsen, Ian;White, Owen;Ralph, Stuart A.;Ren, Qinghu;Sargeant, Tobias J.;Salzberg, Steven L.;Stoeckert, Christian J.;Sullivan, Steven A.;Yamamoto, Marcio M.;Hoffman, Stephen L.;Wortman, Jennifer R.;Gardner, Malcolm J.;Galinski, Mary R.;Barnwell, John W.;Fraser-Liggett, Claire M.
通讯作者：
Fraser-Liggett, Claire M.
影响因子：
5.6
作者：
Khunrae, Pongsak;Philip, Judith M. D.;Bull, Duncan R.;Higgins, Matthew K.
通讯作者：
Higgins, Matthew K.
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
影响因子：
6.1
作者：
Konarev, PV;Volkov, VV;Svergun, DI
通讯作者：
Svergun, DI