Molecular interaction between natural IgG and ficolin--mechanistic insights on adaptive-innate immune crosstalk.
Molecular interaction between natural IgG and ficolin--mechanistic insights on adaptive-innate immune crosstalk.
复制标题
DOI：
10.1038/srep03675
复制
发表时间：
2014-01-14
影响因子：
4.6
通讯作者：
Ding JL
中科院分区：
文献类型：
--
作者：
Panda S;Zhang J;Yang L;Anand GS;Ding JL
最近，我们发现天然IgG（nIgG;适应性免疫的非特异性免疫球蛋白）不是静止的，而是通过与纤维胶凝蛋白（一种先天免疫蛋白）合作在即时免疫防御中起着至关重要的作用。然而，nIgG和纤维胶凝蛋白如何相互作用以及感染期间哪些因素控制复合物的形成尚不清楚。在此，我们发现由感染-炎症状况诱导的轻度酸中毒和低钙血症增加了nIgG：纤维胶凝蛋白复合物的形成。氢-氘交换质谱描绘了与nIgG Fc的CH 2-CH 3区和纤维胶凝蛋白FBG结构域的P-亚结构域的结合界面。感染状况暴露了新的结合位点。定点诱变和表面等离子体共振分析的肽，来自nIgG和纤维胶凝蛋白，定义的蛋白质之间的相互作用的残基。这些结果为代表适应性和先天性免疫途径的两种分子之间的相互作用提供了机理上的见解，促进了可调谐到流行感染条件的免疫调节/预防肽的潜在开发。
Recently, we found that natural IgG (nIgG; a non-specific immunoglobulin of adaptive immunity) is not quiescent, but plays a crucial role in immediate immune defense by collaborating with ficolin (an innate immune protein). However, how the nIgG and ficolin interplay and what factors control the complex formation during infection is unknown. Here, we found that mild acidosis and hypocalcaemia induced by infection- inflammation condition increased the nIgG:ficolin complex formation. Hydrogen-deuterium exchange mass spectrometry delineated the binding interfaces to the CH2–CH3 region of nIgG Fc and P-subdomain of ficolin FBG domain. Infection condition exposes novel binding sites. Site-directed mutagenesis and surface plasmon resonance analyses of peptides, derived from nIgG and ficolin, defined the interacting residues between the proteins. These results provide mechanistic insights on the interaction between two molecules representing the adaptive and innate immune pathways, prompting potential development of immunomodulatory/prophylactic peptides tunable to prevailing infection conditions.
登录
查看更多内容
影响因子：
3.9
作者：
Andersen, Trine;Munthe-Fog, Lea;Jacobsen, Soren
通讯作者：
Jacobsen, Soren
影响因子：
4
作者：
Eichstaedt, Stefanie;Gaebler, Karoline;Hildebrandt, Jar-Peter
通讯作者：
Hildebrandt, Jar-Peter
影响因子：
7.4
作者：
Mandell, JG;Falick, AM;Komives, EA
通讯作者：
Komives, EA
影响因子：
--
作者：
Baranov, Dimitry;Neligan, Patrick
通讯作者：
Neligan, Patrick
影响因子：
4.4
作者：
Martínez, D;Vermeulen, M;Geffner, J
通讯作者：
Geffner, J