Protein Family Models

Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain encompasses macroglobulin-like domain MG5 and 6 including bait region. In Salmonella enterica ser A2Ms, this domain encompasses MG7 and MG8 including the bait region [1] [2]. The Bait region is cleaved by proteases, followed by a large conformational change that blocks the target protease within a cage-like complex. This model of protease entrapment is recognised as the Venus flytrap mechanism [1]. [1]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. [2]. 22290936. The crystal structure of human alpha2-macroglobulin reveals a unique molecular cage. Marrero A, Duquerroy S, Trapani S, Goulas T, Guevara T, Andersen GR, Navaza J, Sottrup-Jensen L, Gomis-Ruth FX;. Angew Chem Int Ed Engl. 2012;51:3340-3344. (from Pfam)

Date:

2024-10-16

This is the MG2 (macroglobulin) domain of alpha-2-macroglobulin in eukaryotes [1]. Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. This domain is found in eukaryotic and bacterial proteins. In human A2Ms, this domain is termed macroglobulin-like (MG) domain 2 and in Salmonella enterica ser A2Ms, this is domain 4 [2] [3]. [1]. 16177781. Structures of complement component C3 provide insights into the function and evolution of immunity. Janssen BJ, Huizinga EG, Raaijmakers HC, Roos A, Daha MR, Nilsson-Ekdahl K, Nilsson B, Gros P;. Nature. 2005;437:505-511. [2]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. [3]. 22290936. The crystal structure of human alpha2-macroglobulin reveals a unique molecular cage. Marrero A, Duquerroy S, Trapani S, Goulas T, Guevara T, Andersen GR, Navaza J, Sottrup-Jensen L, Gomis-Ruth FX;. Angew Chem Int Ed Engl. 2012;51:3340-3344. (from Pfam)

Date:

2024-10-16

This family includes the C-terminal region of the alpha-2-macroglobulin family. [1]. 10625650. NMR solution structure of the receptor binding domain of human alpha(2)-macroglobulin. Huang W, Dolmer K, Liao X, Gettins PG;. J Biol Chem 2000;275:1089-1094. [2]. 11106161. Structure of a rat alpha 1-macroglobulin receptor-binding domain dimer. Xiao T, DeCamp DL, Spran SR;. Protein Sci 2000;9:1889-1897. [3]. 11387479. Structure of complement receptor 2 in complex with its C3d ligand. Szakonyi G, Guthridge JM, Li D, Young K, Holers VM, Chen XS;. Science 2001;292:1725-1728. [4]. 10825534. Structure at 1.44 A resolution of an N-terminally truncated form of the rat serum complement C3d fragment. Zanotti G, Bassetto A, Battistutta R, Folli C, Arcidiaco P, Stoppini M, Berni R;. Biochim Biophys Acta 2000;1478:232-238. (from Pfam)

Date:

2024-10-16

immunoglobulin (Ig)-like domain-containing alpha-2-macroglobulin family protein may be a broad-spectrum protease inhibitor, similar to alpha-2-macroglobulin from Escherichia coli (A2MG, YfhM) and similar proteins from proteobacteria

Date:

2024-10-18