Abstract
Pore-forming proteins play critical roles in pathogenic attack and immunological defence. The membrane attack complex/perforin (MACPF) group of homologues represents, with cholesterol-dependent cytolysins, the largest family of such proteins. In this review, we begin by describing briefly the structure of MACPF proteins, outlining their common mechanism of pore formation. We subsequently discuss some examples of MACPF proteins likely implicated in pore formation or other membrane-remodelling processes. Finally, we focus on astrotactin and bone morphogenetic protein and retinoic acid-induced neural-specific proteins, highly conserved MACPF family members involved in developmental processes, which have not been well studied to date or observed to form a pore—and which data suggest may act by alternative mechanisms.This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.
Highlights
Pore-forming proteins are well known for their roles in pathogenic attack and immunological and other forms of defence, as several of the reviews in this Special Issue attest
We focus on the ASTNs and BRINPs, including description of key features revealed by the first to have its structure solved: ASTN2, a highly conserved protein involved in neuronal development
The sequence identity of the ASTNs is exceptional—to find 53% identity conserved over essentially the whole history of vertebrate life since the Cambrian explosion is striking and suggests the fundamental importance of the roles played by such proteins
Summary
Pore-forming proteins are well known for their roles in pathogenic attack and immunological and other forms of defence, as several of the reviews in this Special Issue attest. The mechanism of pore formation by MACPF/CDC proteins has been thoroughly studied and well established [1,2,3,4]. What has been less intensively studied but is becoming increasingly understood is that MACPF/ CDC proteins are important players in development [5,6], whether these developmental homologues of perforin, complement proteins and bacterial toxins are themselves pore-forming proteins is unknown. We will first give a brief overview on the structure and mechanism of pore formation by MACPF/ CDC proteins and describe their distribution. 2. Structure of membrane attack complex/perforin proteins and mechanism of pore formation. License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited
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