PDBsum entry 2vaa

Complex (mhc i/peptide)

PDB id: 2vaa

Contents

Protein chains

274 a.a. *

99 a.a. *

Ligands

ARG-GLY-TYR-VAL-TYR-GLN-GLY-LEU

Waters ×136

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structures of two viral peptides in complex with murine mhc class i h-2kb.

Authors

D.H.Fremont, M.Matsumura, E.A.Stura, P.A.Peterson, I.A.Wilson.

Ref.

Science, 1992, 257, 919-927. [DOI no: 10.1126/science.1323877]

PubMed id

1323877

Abstract

The x-ray structures of a murine MHC class I molecule (H-2Kb) were determined in complex with two different viral peptides, derived from the vesicular stomatitis virus nucleoprotein (52-59), VSV-8, and the Sendai virus nucleoprotein (324-332), SEV-9. The H-2Kb complexes were refined at 2.3 A for VSV-8 and 2.5 A for SEV-9. The structure of H-2Kb exhibits a high degree of similarity with human HLA class I, although the individual domains can have slightly altered dispositions. Both peptides bind in extended conformations with most of their surfaces buried in the H-2Kb binding groove. The nonamer peptide maintains the same amino- and carboxyl-terminal interactions as the octamer primarily by the insertion of a bulge in the center of an otherwise beta conformation. Most of the specific interactions are between side-chain atoms of H-2Kb and main-chain atoms of peptide. This binding scheme accounts in large part for the enormous diversity of peptide sequences that bind with high affinity to class I molecules. Small but significant conformational changes in H-2Kb are associated with peptide binding, and these synergistic movements may be an integral part of the T cell receptor recognition process.

Secondary reference #1

Title

Crystal structure of an h-2kb-Ovalbumin peptide complex reveals the interplay of primary and secondary anchor positions in the major histocompatibility complex binding groove.

Authors

D.H.Fremont, E.A.Stura, M.Matsumura, P.A.Peterson, I.A.Wilson.

Ref.

Proc Natl Acad Sci U S A, 1995, 92, 2479-2483. [DOI no: 10.1073/pnas.92.7.2479]

PubMed id

7708669

Figure 1.
FIG. 1. Fo-Fc omit electron density map of OVA-8 (SIINFEKL) bound to H-2Kb at 2.5-A resolution contoured at 2.5 ur.

Figure 3.
FIG. 3. OVA-8-associated conformational differences in H-2Kb. The N-terminal regions of OVA-8 (magenta), VSV-8 (yellow), and SEV-9 (cyan) complexes are rendered as tubes. majority of MHC I-peptide interactions are conserved in all three but nevertheless slight variations in the conformation of Glu-63, and especially Trp-167 are observed that apparently result from the differences in the sequences of the bound peptides.

Secondary reference #2

Title

Emerging principles for the recognition of peptide antigens by mhc class i molecules.

Authors

M.Matsumura, D.H.Fremont, P.A.Peterson, I.A.Wilson.

Ref.

Science, 1992, 257, 927-934. [DOI no: 10.1126/science.1323878]

PubMed id

1323878

Secondary reference #3

Title

Crystallization of murine major histocompatibility complex class i h-2kb with single peptides.

Authors

E.A.Stura, M.Matsumura, D.H.Fremont, Y.Saito, P.A.Peterson, I.A.Wilson.

Ref.

J Mol Biol, 1992, 228, 975-982. [DOI no: 10.1016/0022-2836(92)90881-J]

PubMed id

1469730

Figure 1.
Figure 1. Native isoelectri focusing (IEF) gel electro- phoresis of puified H-2Kb molecules. Lane 1, purified H-2Kb alone; lane 2, dissolved crystals of H-2Kb complexed with VSV-8 peptide; lane 3, H-2Kb pre-incu- bated with the VSV-8 peptide (20 P) at 23°C for 4 h in solution. Native IEF (pH 5 o 7) was performed on a mini-IEF apparatus (model 111; BioRad) and silver stained according to the manufacturer's protocol.

Figure 2.
Figure 2. Various crystals obtined for H-2Kb complexes. (a) Flat plate crystals obtained for the H-2K''-VW-8 complex from 20% PEG 4000, 62 iv-imidazole malat (pH 7.0) and 4 mg protein/ml. (b) ``Bushes'' obtained under the same conditions described above predominae. The use of 1 o/o MPD did decrease the prevalence of this unesired form. (c) A ``fuzzy ball'' competes for protein with an X-ray quality triclinic crystal of H-2Kb-VSV-8. These crystals were grown from 18 M-NaH,PG, and K,PO, (pH 6.25), with 0.3% MPD. The presence of MPD decreased the occurrence of the ``fuzzy balls'' to an incidence of 10% to 30% for macroseeded drops. (d) Orthorhombic P2,2,2 crystals for the H-2Kb-VSV-8 complex grown, as above but with 1.5% to 2% MPD. However, the change in surface tension from the MPD addition also enhances undesired effects such as the nuceation at the liquid-glass-air interface (e) and the production of thin sheets at the ar-liquid interface (f). Growth folowing macroseeding of two H-2Kb-SEV-9 crystals into a pre-equilibrated soutions i shown after 6h n (g) and (h). Note the initial growth of thin plates extending from the outside surfaces of the seeded crystal (g). Afer 18h the crystal shown in (h) begins to thicken as well s enlarge (i). These crystls belong to the space group P2,2,2,. (j) Streak seeding of H-2Kb-SEV-9 onto H-2Kb-VSV-8 pre- equilibrated drops demonstrates a strong response. (k) H-2Kb-OVA-8 monoclinic crystal and undesired seeds carried over from the original drop into a new drop. A second streak seeding removed all traces of the undesired forms. (I) Large crystal (pobably triclinic) of the H-2Kb-OVA-8 obtained from PEG 4000.

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