PDBsum entry 1jgd

Immune system

PDB id: 1jgd

Contents

Protein chains

276 a.a. *

100 a.a. *

Ligands

ARG-ARG-LEU-LEU-ARG-GLY-HIS-ASN-GLN-TYR

GOL

Waters ×452

* Residue conservation analysis

PDB id:

1jgd

Name:

Immune system

Title:

Hla-b 2709 Bound to deca-peptide s10r

Structure:

Human lymphocyte antigen hla-b27. Chain: a. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. Peptide s10r. Chain: c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b or hlab. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Other_details: this peptide was chemically synthesized.

Biol. unit:

Trimer (from PQS)

Resolution:

1.90Å R-factor: 0.170 R-free: 0.194

Authors:

R.C.Hillig,M.Huelsmeyer,W.Saenger,A.Volz,B.Uchanska-Ziegler,A.Ziegler

Key ref:

R.C.Hillig et al. (2004). Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association. J Biol Chem, 279, 652-663. PubMed id: 14555655 DOI: 10.1074/jbc.M307457200

Date:

25-Jun-01 Release date: 01-Jul-03

Protein chain

P01889  (1B07_HUMAN) -  HLA class I histocompatibility antigen, B alpha chain from Homo sapiens

Seq: 362 a.a.

Struc: 276 a.a.*

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 100 a.a.*

* PDB and UniProt seqs differ at 21 residue positions (black crosses)

DOI no: 10.1074/jbc.M307457200

J Biol Chem 279:652-663 (2004)

PubMed id: 14555655

Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association.

R.C.Hillig, M.Hülsmeyer, W.Saenger, K.Welfle, R.Misselwitz, H.Welfle, C.Kozerski, A.Volz, B.Uchanska-Ziegler, A.Ziegler.

ABSTRACT

Selected HLA-B27 subtypes are associated with spondyloarthropathies, but the underlying mechanism is not understood. To explain this association in molecular terms, a comparison of peptide-dependent dynamic and structural properties of the differentially disease-associated subtypes HLA-B*2705 and HLA-B*2709 was carried out. These molecules differ only by a single amino acid at the floor of the peptide binding groove. The thermostabilities of a series of HLA-B27 molecules complexed with nonameric and decameric peptides were determined and revealed substantial differences depending on the subtype as well as the residues at the termini of the peptides. In addition we present the crystal structure of the B*2709 subtype complexed with a decameric peptide. This structure provides an explanation for the preference of HLA-B27 for a peptide with an N-terminal arginine as secondary anchor and the lack of preference for tyrosine as peptide C terminus in B*2709. The data show that differences in thermodynamic properties between peptide-complexed HLA-B27 subtypes are correlated with a variety of structural properties.

Selected figure(s)

Figure 2.
FIG. 2. Peptide electron density and differential conformations in the HLA-B27 binding groove. A, electron density map for the s10R peptide (F[o] - F[c] omit map, contoured at 3 , for the final model with the peptide omitted from map calculation). Superimposition of peptide binding grooves of HLA-B27 protein complexes in the top (B) and side view (C) orientation, with the C backbone conformation for s10R (red), m9 (blue, from B^*2709·m9, PDB entry 1k5n [PDB] ; cyan, from B^*2705·m9, PDB entry 1jge [PDB] ), and ARA[7] (yellow, B^*2705·ARA[7], PDB entry 1hsa [PDB] ), illustrating the stronger bulging of s10R out of the binding groove. In C, helix 2 is omitted for clarity.

Figure 7.
FIG. 7. HLA-B27-specific sandwich coordination of the secondary anchor pArg1. A, stereo figure showing the clamp stack involving pArg1 of the s10R peptide (red) and Arg-62, Glu-163, and Trp167 from the HC (green). The alternative conformation of Glu-163 is indicated in light green. Hydrogen bonds between Arg-62, Glu-163, pArg1, and Wat58 are indicated with dotted lines, and - -stacking and hydrophobic interactions by are indicated by stripes. B, the same region in the B^*2709·m9 complex (PDB entry 1jge [PDB] ). Because the N-terminal pArg1 is missing in m9, no stacking is present. Consequently, Trp-167 folds onto pGly1, and the Arg-62 side chain adopts a conformation parallel to helix 1. C and D, for comparison two murine MHC molecules are shown. Both feature a pArg1 but do not adopt the Arg-62-pArg1-Trp-167 sandwich conformation found in B^*2709·s10R. C, H-2Kb·VSV8, PDB entry 1bqh [PDB] , molecule 2. D, H-2D^d·HIV-1 (human immunodeficiency virus 1), PDB entry 1bii [PDB] .

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 652-663) copyright 2004.

Figures were selected by the author.