PDBsum entry 1klu

Immune system/toxin

PDB id: 1klu

Contents

Protein chains

179 a.a. *

190 a.a. *

15 a.a. *

230 a.a. *

Waters ×405

* Residue conservation analysis

PDB id:

1klu

Name:

Immune system/toxin

Title:

Crystal structure of hla-dr1/tpi(23-37) complexed with staphylococcal enterotoxin c3 variant 3b2 (sec3-3b2)

Structure:

Hla class ii histocompatibility antigen, dr alpha chain. Chain: a. Fragment: residues 29-207. Synonym: hla-dr1 alpha subunit. Hla-dr antigen alpha chain. Engineered: yes. Hla class ii histocompatibility antigen, dr-1 beta chain. Chain: b. Fragment: residues 30-219. Synonym: hla-dr1 beta subunit. Hla-dr beta 1 chain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: peptide synthesis. Staphylococcus aureus. Organism_taxid: 1280.

Biol. unit:

Dodecamer (from PQS)

Resolution:

1.93Å R-factor: 0.208 R-free: 0.220

Authors:

E.J.Sundberg,M.W.Sawicki,P.S.Andersen,J.Sidney,A.Sette,R.A.Mariuzza

Key ref:

E.J.Sundberg et al. (2002). Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line. J Mol Biol, 319, 449-461. PubMed id: 12051920 DOI: 10.1016/S0022-2836(02)00370-4

Date:

12-Dec-01 Release date: 02-Aug-02

Protein chain

P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain from Homo sapiens

Seq: 254 a.a.

Struc: 179 a.a.

Protein chain

P01911  (2B1F_HUMAN) -  HLA class II histocompatibility antigen, DRB1 beta chain from Homo sapiens

Seq: 266 a.a.

Struc: 190 a.a.*

Protein chain

P60174  (TPIS_HUMAN) -  Triosephosphate isomerase from Homo sapiens

Seq: 249 a.a.

Struc: 15 a.a.

Protein chain

P0A0L5  (ENTC3_STAAU) -  Enterotoxin type C-3 from Staphylococcus aureus

Seq: 266 a.a.

Struc: 230 a.a.*

* PDB and UniProt seqs differ at 17 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain C: E.C.4.2.3.3 - methylglyoxal synthase.
• Reaction: dihydroxyacetone phosphate = methylglyoxal + phosphate
• Enzyme class 3: Chain C: E.C.5.3.1.1 - triose-phosphate isomerase.
• Reaction: D-glyceraldehyde 3-phosphate = dihydroxyacetone phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0022-2836(02)00370-4

J Mol Biol 319:449-461 (2002)

PubMed id: 12051920

Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line.

E.J.Sundberg, M.W.Sawicki, S.Southwood, P.S.Andersen, A.Sette, R.A.Mariuzza.

ABSTRACT

While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies.

Selected figure(s)

Figure 1.
Figure 1. The wild-type and mutant TPI[23-37] peptide/HLA-DR1/SEC3-3B2 complex structures. s[A]-Weighted 2F[o] -F[c] electron density maps in which the TPI[23-37] peptide atoms have been omitted from the map calculation for (a) the wild-type TPI[23-37] peptide and (b) the mutant TPI[23-37] peptide. Maps are contoured at 1.0s. (c) Superposition of the overall wild-type and mutant TPI[23-37] peptide/HLA-DR1/SEC3-3B2 complex structures. In all panels, colors are as follows: wild-type TPI[23-37] peptide, yellow; mutant TPI[23-37] peptide, green; HLA-DR1 a chain, purple; HLA-DR1 b chain, cyan; SEC3-3B2, red; nitrogen atoms, blue; oxygen atoms and water molecules, red. (a) and (b) produced using Bobscript[61] and Raster3D. [62] (c) and subsequent Figures produced using MOLSCRIPT [63] and Raster3D, [62] unless otherwise noted.

Figure 4.
Figure 4. Very similar molecular surfaces are presented to the T cell receptor by HLA-DR1 complexed with both the wild-type and mutant TPI[23-37] peptides. Molecular surface of HLA-DR1 complexed with (a) the wild-type TPI[23-37] peptide and (b) the mutant TPI[23-37] peptide. Color coding is as follows: green, carbon atoms; magenta, uncharged polar atoms; red, electronegative atoms; blue, electropositive atoms. The mutation site is outlined in black. Figure produced using GRASP.[64]

The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 319, 449-461) copyright 2002.

Figures were selected by an automated process.