4HWJ

Crystal Structure of the Human C3a desArg anaphylatoxin

4HWJ の概要

• エントリーDOI: 10.2210/pdb4hwj/pdb
• 関連するPDBエントリー: 4HW5
• 分子名称: Complement C3, SULFATE ION (3 entities in total)
• 機能のキーワード: complement system, anaphylatoxins, inflammation, c3a, c3a desarg, innate immunity, four-helix-bundle, c5a, c5a desarg, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01024
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9437.99

構造登録者

Bajic, G.,Yatime, L.,Andersen, G.R. (登録日: 2012-11-08, 公開日: 2012-12-12, 最終更新日: 2018-03-07)

主引用文献

Bajic, G.,Yatime, L.,Klos, A.,Andersen, G.R.
Human C3a and C3a desArg anaphylatoxins have conserved structures, in contrast to C5a and C5a desArg.
Protein Sci., 22:204-212, 2013

PubMed Abstract: Complement is a part of innate immunity that has a critical role in the protection against microbial infections, bridges the innate with the adaptive immunity and initiates inflammation. Activation of the complement, by specific recognition of molecular patterns presented by an activator, for example, a pathogen cell, in the classical and lectin pathways or spontaneously in the alternative pathway, leads to the opsonization of the activator and the production of pro-inflammatory molecules such as the C3a anaphylatoxin. The biological function of this anaphylatoxin is regulated by carboxypeptidase B, a plasma protease that cleaves off the C-terminal arginine yielding C3a desArg, an inactive form. While functional assays demonstrate strikingly different physiological effects between C3a and C3a desArg, no structural information is available on the possible conformational differences between the two proteins. Here, we report a novel and simple expression and purification protocol for recombinant human C3a and C3a desArg anaphylatoxins, as well as their crystal structures at 2.3 and 2.6 Å, respectively. Structural analysis revealed no significant conformational differences between the two anaphylatoxins in contrast to what has been reported for C5a and C5a desArg. We compare the structures of different anaphylatoxins and discuss the relevance of their observed conformations to complement activation and binding of the anaphylatoxins to their cognate receptors.

PubMed: 23184394
DOI: 10.1002/pro.2200

実験手法

X-RAY DIFFRACTION (2.6 Å)