PDBsum entry 1tmc

Histocompatibility antigen

PDB id: 1tmc

Contents

Protein chains

175 a.a. *

99 a.a. *

Ligands

GLU-VAL-ALA-PRO-PRO-GLU-TYR-HIS-ARG-LYS

Waters ×98

* Residue conservation analysis

References listed in PDB file

Key reference

Title

The three-Dimensional structure of a class i major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain.

Authors

E.J.Collins, D.N.Garboczi, M.N.Karpusas, D.C.Wiley.

Ref.

Proc Natl Acad Sci U S A, 1995, 92, 1218-1221. [DOI no: 10.1073/pnas.92.4.1218]

PubMed id

7862664

Abstract

Class I major histocompatibility complex (MHC) molecules are ternary complexes of the soluble serum protein beta 2-microglobulin, MHC heavy chain, and bound peptide. The first two domains (alpha 1, alpha 2) of the heavy chain create the peptide binding cleft and the surface that contacts the T-cell receptor. The third domain (alpha 3) associates with the T-cell co-receptor, CD8, during T-cell recognition. Here we describe the x-ray crystal structure of a human class I MHC molecule, HLA-Aw68, from which the alpha 3 domain has been proteolytically removed. The resulting molecule shows no gross morphological changes compared to the intact protein. A decameric peptide complexed with the intact HLA-Aw68 is seen to bind to the proteolized molecule in the conventional manner, demonstrating that the alpha 3 domain is not required for the structural integrity of the molecule or for peptide binding.

Secondary reference #1

Title

Five viral peptide-Hla-A2 co-Crystals. Simultaneous space group determination and X-Ray data collection.

Authors

D.N.Garboczi, D.R.Madden, D.C.Wiley.

Ref.

J Mol Biol, 1994, 239, 581-587.

PubMed id

7516439

Secondary reference #2

Title

The antigenic identity of peptide-Mhc complexes: a comparison of the conformations of five viral peptides presented by hla-A2.

Authors

D.R.Madden, D.N.Garboczi, D.C.Wiley.

Ref.

Cell, 1993, 75, 693-708. [DOI no: 10.1016/0092-8674(93)90490-H]

PubMed id

7694806

Secondary reference #3

Title

Comparison of the p2 specificity pocket in three human histocompatibility antigens: hla-A6801, Hla-A0201, And hla-B2705.

Authors

H.C.Guo, D.R.Madden, M.L.Silver, T.S.Jardetzky, J.C.Gorga, J.L.Strominger, D.C.Wiley.

Ref.

Proc Natl Acad Sci U S A, 1993, 90, 8053-8057. [DOI no: 10.1073/pnas.90.17.8053]

PubMed id

8367462

Secondary reference #4

Title

Different length peptides bind to hla-Aw68 similarly at their ends but bulge out in the middle.

Authors

H.C.Guo, T.S.Jardetzky, T.P.Garrett, W.S.Lane, J.L.Strominger, D.C.Wiley.

Ref.

Nature, 1992, 360, 364-366.

PubMed id

1448153

Secondary reference #5

Title

Hla-A2-Peptide complexes: refolding and crystallization of molecules expressed in escherichia coli and complexed with single antigenic peptides.

Authors

D.N.Garboczi, D.T.Hung, D.C.Wiley.

Ref.

Proc Natl Acad Sci U S A, 1992, 89, 3429-3433. [DOI no: 10.1073/pnas.89.8.3429]

PubMed id

1565634

Secondary reference #6

Title

Refined structure of the human histocompatibility antigen hla-A2 at 2.6 a resolution.

Authors

M.A.Saper, P.J.Bjorkman, D.C.Wiley.

Ref.

J Mol Biol, 1991, 219, 277-319.

PubMed id

2038058

Secondary reference #7

Title

Structure of the human class I histocompatibility antigen, Hla-A2.

Authors

P.J.Bjorkman, M.A.Saper, B.Samraoui, W.S.Bennett, J.L.Strominger, D.C.Wiley.

Ref.

Nature, 1987, 329, 506-512. [DOI no: 10.1038/329506a0]

PubMed id

3309677

Figure 2.
Fig 2. Schematic representation of the structure of HLA-A2.

Figure 6.
Fig 6. Van der Waals surface representation of the top of the HLA-A2 molecules (a) showing the deep groove identified as the antigen recognition site ans the electron density (b) found in this site in crystals of HLA-A2.

The above figures are reproduced from the cited reference with permission from Macmillan Publishers Ltd

Secondary reference #8

Title

The foreign antigen binding site and t cell recognition regions of class i histocompatibility antigens.

Authors

P.J.Bjorkman, M.A.Saper, B.Samraoui, W.S.Bennett, J.L.Strominger, D.C.Wiley.

Ref.

Nature, 1987, 329, 512-518.

PubMed id

2443855

Secondary reference #9

Title

Crystallization and X-Ray diffraction studies on the histocompatibility antigens hla-A2 and hla-A28 from human cell membranes.

Authors

P.J.Bjorkman, J.L.Strominger, D.C.Wiley.

Ref.

J Mol Biol, 1985, 186, 205-210. [DOI no: 10.1016/0022-2836(85)90271-2]

PubMed id

3878413

Figure 1.
Figure 1. Comparison of P2, and P2,2,2, transforms. Upper left: A 6'' screened precession photograph taken from a 1'2, crystal with the X-ray beam parallel to the monoclinic [102] axis. Upper right: A 6'' screened precession photograph taken from a P2,2,2, crystal with the X-ray beam parallel to the orthorhombic c axis (MO). Lower left: The 2 photographs are superimposed to demonstrate that the reciprocal lattices are sampled in identical position. Lower right: The 2 photographs are superimposed, but offset slightly. to demonstrate that the 2 reciprocal lattices have similar intensity distributions.

Figure 3.
Figure 3. Proposed model for the domain organization of HLA-A. Crystallographic evidence suggests that the molecule is approximately 2-fold symmetric, implying that the homologous domains of HLA are paired al to ~2, and cr3 to /?,-micoglobulin (/&m). This pairing of domains has been suggested, based on the similarities between class I and class II antigens (see e.g. Kaufman et al., 1984).

The above figures are reproduced from the cited reference with permission from Elsevier