|SMART accession number:||SM01360|
|Description:||This family includes the C-terminal region of the alpha-2-macroglobulin family.|
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- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing A2M domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with A2M domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing A2M domain in the selected taxonomic class.
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Szakonyi G, Guthridge JM, Li D, Young K, Holers VM, Chen XS
- Structure of complement receptor 2 in complex with its C3d ligand.
- Science. 2001; 292: 1725-8
- Display abstract
Complement receptor 2 (CR2/CD21) is an important receptor that amplifies Blymphocyte activation by bridging the innate and adaptive immune systems. CR2ligands include complement C3d and Epstein-Barr virus glycoprotein 350/220. Wedescribe the x-ray structure of this CR2 domain in complex with C3d at 2.0angstroms. The structure reveals extensive main chain interactions between C3dand only one short consensus repeat (SCR) of CR2 and substantial SCR side-sidepacking. These results provide a detailed understanding of receptor-ligandinteractions in this protein family and reveal potential target sites formolecular drug design.
- Huang W, Dolmer K, Liao X, Gettins PG
- NMR solution structure of the receptor binding domain of humanalpha(2)-macroglobulin.
- J Biol Chem. 2000; 275: 1089-94
- Display abstract
Human alpha(2)-macroglobulin-proteinase complexes bind to their receptor, the lowdensity lipoprotein receptor-related protein (LRP), through a discrete138-residue C-terminal receptor binding domain (RBD), which also binds to thebeta-amyloid peptide. We have used NMR spectroscopy on recombinantly expresseduniformly (13)C/(15)N-labeled human RBD to determine its three-dimensionalstructure in solution. Human RBD is a sandwich of two antiparallel beta-sheets,one four-strand and one five-strand, and also contains one alpha-helix of 2.5turns and an additional 1-turn helical region. The principal alpha-helix containstwo lysine residues on the outer face that are known to be essential for receptorbinding. A calcium binding site (K(d) approximately 11 mM) is present in the loopregion at one end of the beta-sandwich. Calcium binding principally affects this loop region and does not significantly perturb the stable core structure of thedomain. The structure and NMR assignments will enable us to examine in solutionspecific binding of RBD to domains of the receptor and to beta-amyloid peptide.
- Xiao T, DeCamp DL, Sprang SR
- Structure of a rat alpha(1)-macroglobulin receptor-binding domain dimer.
- Protein Sci. 2000; 9: 1889-97
- Display abstract
Alpha-macroglobulin inhibits a broad spectrum of proteinases by formingmacromolecular cages inside which proteinases are cross-linked and trapped. Upon formation of a complex with proteinase, alpha-macroglobulin undergoes a largeconformational change that results in the exposure of its receptor-binding domain(RBD). Engagement of this domain by alpha-macroglobulin receptor permitsclearance of the alpha-macroglobulin: proteinase complex from circulation. Thecrystal structure of rat alpha1-macroglobulin RBD has been determined at 2.3 Aresolution. The RBD is composed of a nine-stranded beta-sandwich and a singlealpha-helix that has been implicated as part of the receptor binding site andthat lies on the surface of the beta-sandwich. The crystallographic asymmetricunit contains a dimer of RBDs related by approximate twofold symmetry such thatthe putative receptor recognition sites of the two monomers are contiguous. Bygel filtration and ultracentrifugation, it is shown that RBD dimers form insolution with a dissociation constant of approximately 50 microM. The structureof the RBD dimer might mimic a conformation of transformed alpha-macroglobulin inwhich the proposed receptor binding residues are exposed on one face of thedimer. A pair of phenylalanine residues replaces a cystine that is conserved inother members of the macroglobulin family. These residues participate in anetwork of aromatic side-chain interactions that appears to stabilize the dimerinterface.
- Zanotti G et al.
- Structure at 1.44 A resolution of an N-terminally truncated form of the rat serumcomplement C3d fragment.
- Biochim Biophys Acta. 2000; 1478: 232-8
- Display abstract
Complement component C3 plays a key role in the complement-mediated immunedefence, and occupies a central position within the complement cascade system.One of its degradation products, C3dg, was purified from rat serum andcrystallised in two different crystal forms as N-terminally truncated fragment.Despite the truncation and the lack of a significant portion of the N-terminus ascompared to C3d, the structure of the fragment is highly similar to that ofrecombinant human C3d (Nagar et al., Science 280 (1998) 1277-1281). Structuraldetails of the reactive site have been obtained, suggesting a possible mode ofthioester bond formation between Cys-1010 and Gln-1013 and thioester bondcleavage in the transacylation reaction involving His-1126. The truncation at theN-terminus of C3d leads to the exposure of a surface of the molecule that favoursdimerisation, so that in both crystal forms, the fragment is present as a dimer, with monomers related by a two-fold axis.
- Structure (3D structures containing this domain)
3D Structures of A2M domains in PDB
PDB code Main view Title 2a73 Human Complement Component C3 2a74 Human Complement Component C3c 2b39 Structure of mammalian C3 with an intact thioester at 3A resolution 2hr0 Structure of Complement C3b: Insights into Complement Activation and Regulation 2i07 Human Complement Component C3b 2ice CRIg bound to C3c 2icf CRIg bound to C3b 2pn5 Crystal Structure of TEP1r 2qki Human C3c in complex with the inhibitor compstatin 2wii Complement C3b in complex with factor H domains 1-4 2win C3 convertase (C3bBb) stabilized by SCIN 2xwb Crystal Structure of Complement C3b in complex with Factors B and D 2xwj Crystal Structure of Complement C3b in Complex with Factor B 3cu7 Human Complement Component 5 3frp Crystal Structure of Cobra Venom Factor, a Co-factor for C3- and C5 convertase CVFBb 3g6j C3b in complex with a C3b specific Fab 3hrz Cobra Venom Factor (CVF) in complex with human factor B 3hs0 Cobra Venom Factor (CVF) in complex with human factor B 3kls Structure of complement C5 in complex with SSL7 3km9 Structure of complement C5 in complex with the C-terminal beta-grasp domain of SSL7 3l3o Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement Component C3c 3l5n Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement Component C3b 3nms Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement C3c 3ohx Molecular Basis for Complement Recognition and Inhibition Determined by Crystallographic Studies of the Staphylococcal Complement Inhibitor (SCIN) Bound to C3c and C3b 3prx Structure of Complement C5 in Complex with CVF and SSL7 3pvm Structure of Complement C5 in Complex with CVF 3t4a Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution 4a5w Crystal structure of C5b6 4acq Alpha-2 Macroglobulin 4d94 Crystal Structure of TEP1r 4e0s Crystal Structure of C5b-6 4fxg Complement C4 in complex with MASP-2 4fxk Human complement C4 4lnv Crystal Structure of TEP1s
- Links (links to other resources describing this domain)