title: Crystal structure of a bony fish beta2-microglobulin: insights into the evolutionary origin of immunoglobulin superfamily constant molecules.
abstract: Three-dimensional structures of beta(2)-microglobulin (beta2m) from chicken and various mammals have been described previously, but aside from genomic sequences, very little is known about the three-dimensional structures of beta2m in species other than warm-blooded vertebrates. Here, we present the first three-dimensional structure of beta2m from bony fish grass carp (Ctid-beta2m), resolved at 2.1 A. The key structural differences between this new structure and previously published structures are two new hydrogen bonds at positions Ile(37) and Glu(38) in strand C and Lys(66) in strand E, and a hydrophobic pocket around the center of the protein found in Ctid-beta2m. Importantly, Ctid-beta2m has a short D strand and a long loop between stands C and D, rather than the flexible region found in other beta2m structures that serves as a putative binding region for the major histocompatibility complex heavy chain. Comparing the Ctid-beta2m structure with those of bovine and human beta2ms, the Calpha root mean square deviation of the latter are 1.3 A and 1.8 A, respectively. Compared with the constant domains of Lamprey T cell receptor-like receptor (Lamp-TCRLC) and Amphioxus V and C domain-bearing protein (Amphi-VCPC), Ctid-beta2m exhibits very different topology. The three-dimensional structures of domains predicted from Amphi-VCPC/Lamp-TCRLC are distinctly lacking in strand A of beta2ms. There are 18 amino acids at the N terminus of Amphi-VCPC that may have evolved into strand A of beta2ms. A mutation in the BC loops of Amphi-VCPC may have led to the novel topology found in beta2m. Based on these results, Ctid-beta2m may well reflect evolutionary characteristics of ancestral C set molecules.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Fuliang
authors.initials: F
authors.lastname: Chu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.forename: Chun
authors.initials: C
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002347:Carps / Q000378:metabolism*; D002417:Cattle; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006801:Humans; D006860:Hydrogen Bonding; D007127:Immunoglobulin Constant Regions / Q000737:chemistry*; D007798:Lampreys; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein; D001613:beta 2-Microglobulin / Q000737:chemistry*
chemical_list: D007127:Immunoglobulin Constant Regions; D001613:beta 2-Microglobulin
references.citation: J Immunol. 2004 Mar 15;172(6):3635-43
references.pmid: 15004166
references.citation: J Immunol. 2007 Jan 15;178(2):944-52
references.pmid: 17202356
references.citation: Proc Natl Acad Sci U S A. 1985 Jun;82(12):4225-9
references.pmid: 3889925
references.citation: Immunity. 1996 Mar;4(3):215-28
references.pmid: 8624812
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
references.pmid: 9757107
references.citation: Biochim Biophys Acta. 2005 Nov 10;1753(1):85-91
references.pmid: 16084780
references.citation: Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9
references.pmid: 2025413
references.citation: Nat Immunol. 2006 Aug;7(8):875-82
references.pmid: 16799561
references.citation: Proc Natl Acad Sci U S A. 1979 Aug;76(8):3844-8
references.pmid: 91170
references.citation: Immunity. 1998 Aug;9(2):199-208
references.pmid: 9729040
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2754-9
references.pmid: 11880627
references.citation: Nature. 1987 Oct 8-14;329(6139):506-12
references.pmid: 3309677
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9771-6
references.pmid: 12119416
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Mar 1;64(Pt 3):200-2
references.pmid: 18323608
references.citation: Protein Expr Purif. 2007 Jan;51(1):120-5
references.pmid: 17005417
references.citation: J Mol Biol. 1994 Sep 30;242(4):309-20
references.pmid: 7932691
references.citation: Immunogenetics. 1999 Oct;50(1-2):49-59
references.pmid: 10541806
references.citation: Immunogenetics. 1999 Oct;50(1-2):79-83
references.pmid: 10541811
references.citation: Immunogenetics. 1993;38(1):1-10
references.pmid: 8462988
references.citation: Cell. 2006 Feb 24;124(4):815-22
references.pmid: 16497590
references.citation: J Immunol. 2005 Mar 15;174(6):3493-500
references.pmid: 15749885
references.citation: Nature. 2007 Feb 15;445(7129):732-7
references.pmid: 17301785
references.citation: Immunogenetics. 1998 Oct;48(5):339-43
references.pmid: 9745011
references.citation: J Immunol. 2001 Jun 15;166(12):7327-34
references.pmid: 11390483
references.citation: J Mol Biol. 1993 Jun 20;231(4):1049-67
references.pmid: 8515464
references.citation: J Biol Chem. 2006 Nov 24;281(47):36378-90
references.pmid: 17005555
references.citation: Immunogenetics. 1993;38(1):27-34
references.pmid: 8462991
references.citation: Fish Shellfish Immunol. 2006 Jan;20(1):118-23
references.pmid: 15951200
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13273-8
references.pmid: 15328402
references.citation: Immunity. 2007 Dec;27(6):885-99
references.pmid: 18083574