Action of the Terminal Complement Pathway on Cell Membranes.

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bill H T Ho, Bradley A Spicer, Michelle A Dunstone
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引用次数: 0

Abstract

The complement pathway is one of the most ancient elements of the host's innate response and includes a set of protein effectors that rapidly react against pathogens. The late stages of the complement reaction are broadly categorised into two major outcomes. Firstly, C5a receptors, expressed on membranes of host cells, are activated by C5a to generate pro-inflammatory responses. Secondly, target cells are lysed by a hetero-oligomeric pore known as the membrane attack complex (MAC) that punctures the cellular membrane, causing ion and osmotic flux. Generally, several membrane-bound and soluble inhibitors protect the host membrane from complement damage. This includes inhibitors against the MAC, such as clusterin and CD59. This review addresses the most recent molecular and structural insights behind the activation and modulation of the integral membrane proteins, the C5a receptors (C5aR1 and C5aR2), as well as the regulation of MAC assembly. The second aspect of the review focuses on the molecular basis behind inflammatory diseases that are reflective of failure to regulate the terminal complement effectors. Although each arm is unique in its function, both pathways may share similar outcomes in these diseases. As such, the review outlines potential synergy and crosstalk between C5a receptor activation and MAC-mediated cellular responses.

终末补体途径对细胞膜的作用。
补体途径是宿主先天反应中最古老的元素之一,包括一组快速对抗病原体的蛋白质效应器。补体反应的后期大致分为两种主要结果。首先,宿主细胞膜上表达的C5a受体被C5a激活,产生促炎反应。其次,靶细胞被称为膜攻击复合物(MAC)的异聚寡聚孔裂解,该孔刺穿细胞膜,引起离子和渗透通量。通常,几种膜结合和可溶性抑制剂保护宿主膜免受补体损伤。这包括抗MAC的抑制剂,如clusterin和CD59。本文综述了完整膜蛋白C5a受体(C5aR1和C5aR2)的激活和调节以及MAC组装的最新分子和结构见解。回顾的第二个方面侧重于炎性疾病背后的分子基础,这些疾病反映了末端补体效应物调节失败。尽管每个分支的功能都是独特的,但这两种途径在这些疾病中可能具有相似的结果。因此,本文概述了C5a受体激活和mac介导的细胞反应之间潜在的协同作用和串扰。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Membrane Biology
Journal of Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
4.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.
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