Protein Family Models

Bacterial alpha-2 macroglobulin (A2M) are located in the periplasm and may protect the cell by trapping external proteases through a covalent interaction with an activated thioester [1,2]. Macroglobulin (MG) beta sandwich domains appear to play a structural role. This entry represents bacterial MG2 (bMG2) domain which, with MG1, plays the role of a linker associating the main body of A2M to the bilayer [1-3]. Paper describing PDB structure 4rtd. [1]. 26143919. Structure of protease-cleaved Escherichia coli alpha-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment. Fyfe CD, Grinter R, Josts I, Mosbahi K, Roszak AW, Cogdell RJ, Wall DM, Burchmore RJ, Byron O, Walker D;. Acta Crystallogr D Biol Crystallogr. 2015;71:1478-1486. Paper describing PDB structure 4u48. [2]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. Paper describing PDB structure 4ziq. [3]. 26100869. Structural and functional insights into Escherichia coli alpha2-macroglobulin endopeptidase snap-trap inhibition. Garcia-Ferrer I, Arede P, Gomez-Blanco J, Luque D, Duquerroy S, Caston JR, Goulas T, Gomis-Ruth FX;. Proc Natl Acad Sci U S A. 2015;112:8290-8295. (from Pfam)

Date:

2024-10-16

This macroglobulin domain is found in bacterial alpha 2 macroglobulin proteins. It adopts an Ig-like beta sandwich fold [1]. [1]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. (from Pfam)

Date:

2024-10-16

This domain is found in a group of proteins predominantly found in proteobacteria, including Alpha-2-macroglobulin (A2MG) from Salmonella typhimurium, a protein that protects the bacterial cell from host peptidases. A2MG is composed of 13 domains, 12 of them folding as beta sandwiches. This entry represents the CUB (complement C1r/C1s, Uegf, Bmp1) domain, which is connected to the TED domain (Pfam:PF07678). Paper describing PDB structure 4rtd. [1]. 26143919. Structure of protease-cleaved Escherichia coli alpha-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment. Fyfe CD, Grinter R, Josts I, Mosbahi K, Roszak AW, Cogdell RJ, Wall DM, Burchmore RJ, Byron O, Walker D;. Acta Crystallogr D Biol Crystallogr. 2015;71:1478-1486. Paper describing PDB structure 4u48. [2]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. Paper describing PDB structure 4ziq. [3]. 26100869. Structural and functional insights into Escherichia coli alpha2-macroglobulin endopeptidase snap-trap inhibition. Garcia-Ferrer I, Arede P, Gomez-Blanco J, Luque D, Duquerroy S, Caston JR, Goulas T, Gomis-Ruth FX;. Proc Natl Acad Sci U S A. 2015;112:8290-8295. (from Pfam)

Date:

2024-10-16

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. Bacterial A2Ms are located in the periplasm where they are believed to provide protection to the cell by trapping external proteases through a covalent interaction with an activated thioester. This domain is found on the N-terminal region in A2Ms in bacteria. Structure analysis of Salmonella enterica ser A2Ms (SA-A2Ms) show that they are composed of 13 domains, all of which fold as variants of beta sandwiches with the exception of the TED, which consists of 14 alpha helices. Most of the beta sandwich domains appear to serve a structural role and are referred to as the macroglobulin-like (MG) domains. This is the MG5 domain [1]. [1]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. (from Pfam)

Date:

2024-10-16

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. Bacterial A2Ms are located in the periplasm where they are believed to provide protection to the cell by trapping external proteases through a covalent interaction with an activated thioester. This domain is found on the N-terminal region in A2Ms in bacteria. Structure analysis of Salmonella enterica ser A2Ms (SA-A2Ms) show that they are composed of 13 domains, all of which fold as variants of beta sandwiches with the exception of the TED, which consists of 14 alpha helices. Most of the beta sandwich domains appear to serve a structural role and are referred to as the macroglobulin-like (MG) domains. This is the MG1 domain which is the farthest from the body of the structure. It is normally anchored to the inner membrane in vivo and connected to MG2 by a flexible linker [1]. [1]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. (from Pfam)

Date:

2024-10-16

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. Bacterial A2Ms are located in the periplasm where they are believed to provide protection to the cell by trapping external proteases through a covalent interaction with an activated thioester. This domain is found on the C-terminal region in A2Ms in bacteria. Structure analysis of Salmonella enterica ser A2Ms (SA-A2Ms) show that they are composed of 13 domains, all of which fold as variants of beta sandwiches with the exception of the TED, which consists of 14 alpha helices. Most of the beta sandwich domains appear to serve a structural role and are referred to as the macroglobulin-like (MG) domains. This is the MG10 domain. MG10 is markedly different from the other MG domains in that it has more beta strands and an alpha helix. The position of MG10 is stabilized by, in addition to other hydrogen bonds, the formation of a beta sheet with MG9 [1]. [1]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. (from Pfam)

Date:

2024-10-16

This is the MG3 domain from bacterial alpha2-macroglobulins [1]. [1]. 25221932. Structure of a bacterial alpha2-macroglobulin reveals mimicry of eukaryotic innate immunity. Wong SG, Dessen A;. Nat Commun. 2014;5:4917. (from Pfam)

Date:

2024-10-16

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 entry corresponds to the TED domain of the complement components such as C3, C4 and C5. This domain contains a short highly conserved region of proteinase-binding alpha-macro-globulins contains the cysteine and a glutamine of a thiol-ester bond that is cleaved at the moment of proteinase binding, and mediates the covalent binding of the alpha-macro-globulin to the proteinase. The GCGEQ motif is highly conserved. [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

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