PDBsum entry 2hla

Histocompatibility antigen

PDB id: 2hla

Contents

Protein chains

270 a.a. *

99 a.a. *

Waters ×10

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Specificity pockets for the side chains of peptide antigens in hla-Aw68.

Authors

T.P.Garrett, M.A.Saper, P.J.Bjorkman, J.L.Strominger, D.C.Wiley.

Ref.

Nature, 1989, 342, 692-696.

PubMed id

2594067

Abstract

We have determined the structure of a second human histocompatibility glycoprotein, HLA-Aw68, by X-ray crystallography and refined it to a resolution of 2.6 A. Overall, the structure is extremely similar to that of HLA-A2 (refs 1, 2; and M.A.S. et al., manuscript in preparation), although the 11 amino-acid substitutions at polymorphic residues in the antigen-binding cleft alter the detailed shape and electrostatic charge of that site. A prominent negatively charged pocket within the cleft extends underneath the alpha-helix of the alpha 1-domain, providing a potential subsite for recognizing a positively charged side chain or peptide N terminus. Uninterpreted electron density, presumably representing an unknown 'antigen(s)', which seems to be different from that seen in the HLA-A2 structure, occupies the cleft and extends into the negatively charged pocket in HLA-Aw68. The structures of HLA-Aw68 and HLA-A2 demonstrate how polymorphism creates and alters subsites (pockets) positioned to bind peptide side chains, thereby suggesting the structural basis for allelic specificity in foreign antigen binding.

Secondary reference #1

Title

Authors

T.P.J.Garrett, M.A.Saper, D.C.Wiley.

Ref.

TO BE PUBLISHED ...

Secondary reference #2

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 #3

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 #4

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