PDBsum entry 1k2d

Immune system

PDB id: 1k2d

Contents

Protein chains

182 a.a. *

185 a.a. *

12 a.a. *

Ligands

NAG ×3

Waters ×450

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of mbp complexed with i-Au.

Authors

X.L.He, C.Radu, J.Sidney, A.Sette, E.S.Ward, K.C.Garcia.

Ref.

Immunity, 2002, 17, 83-94. [DOI no: 10.1016/S1074-7613(02)00340-0]

PubMed id

12150894

Abstract

Murine experimental allergic encephalomyelitis (EAE) is a useful model for the demyelinating, autoimmune disease multiple sclerosis. In the EAE system, the immunodominant N-terminal epitope of myelin basic protein (MBP) is an unusually short, weakly binding peptide antigen which elicits highly biased TCR chain usage. In the 2.2 A crystal structure of I-A(u)/MBP1-11 complex, only MBP residues 1-7 are bound toward one end of the peptide binding cleft. The fourth residue of MBP1-11 is located in an incompatible p6 pocket of I-A(u), thus explaining the short half-life of I-A(u) complexed with Ac1-11. MBP peptides extended at the C terminus of Ac1-11 result in dramatic affinity increases, likely attributed to register shifting to a higher affinity cryptic epitope, which could potentially mask the presentation of the immunodominant MBP1-11 peptide during thymic education.

Figure 2.
Figure 2. Molecular Surface Complementarity between the I-A^u Groove and the MBP PeptideTo depict the natural Ac-11 peptide, the residual leader peptide residues have been removed from the structure. Molecular surfaces of I-A^u (blue) with bound MBP peptide (purple) were produced, and the figures show planar cross sections through these surfaces to illustrate the shape and complementarity between peptide and MHC, as well as unfilled pockets and ordered water molecules (red spheres). The MBP peptide is shown within the surface as silver sticks. (A) is a side view, as in Figure 1C, and (B) is the groove viewed from the top, as in Figure 1D. Due to the planar cross section of the convoluted surfaces, some residues of the peptide are sliced out of view, such as P5-Arg, which extends toward the reader in (A) and (B). In (A), the large and spacious p6 pocket is apparent, as are the ordered water molecules in the p1 and p6 pockets. In (B), the empty p1 pocket is in the far left of the blue I-A^u molecular surface, and the p7 pocket, where the P5-Arg resides, extends sideways but does not appear occupied by P5-Arg due to the cross section. The molecular surfaces were produced using a 1.4 Å probe radius.

Figure 3.
Figure 3. MBP Peptide Interactions with I-A^uThe orientation is as for the side view shown in Figure 1, with the peptide (purple) N terminus to the left and C terminus to the right. I-A^u β chain helix is in front (gray tube), and α chain helix is in back (gray) of the peptide. The residues of I-A^u which interact with the peptide are drawn as cyan. H bonds are indicated as green dots. Relevant residues are labeled for the (A) N-terminal, (B) central, and (C) more C-terminal MBP peptide interactions with I-A^u.

The above figures are reprinted by permission from Cell Press: Immunity (2002, 17, 83-94) copyright 2002.