Whether T-cell receptors (TCRs) recognize antigenic peptides bound to major histocompatability complex (MHC) molecules through common or distinct docking modes is currently uncertain. We report the crystal structure of a complex between the murine N15 TCR [1-4] and its peptide-MHC ligand, an octapeptide fragment representing amino acids 52-59 of the vesicular stomatitis virus nuclear capsid protein (VSV8) bound to the murine H-2Kb class I MHC molecule. Comparison of the structure of the N15 TCR-VSV8-H-2Kb complex with the murine 2C TCR-dEV8-H-2Kb [5] and the human A6 TCR-Tax-HLA-A2 [6] complexes revealed a common docking mode, regardless of TCR specificity or species origin, in which the TCR variable Valpha domain overlies the MHC alpha2 helix and the Vbeta domain overlies the MHC alpha1 helix. As a consequence, the complementary determining regions CDR1 and CDR3 of the TCR Valpha and Vbeta domains make the major contacts with the peptide, while the CDR2 loops interact primarily with the MHC. Nonetheless, in terms of the details of the relative orientation and disposition of binding, there is substantial variation in TCR parameters, which we term twist, tilt and shift, and which define the variation of the V module of the TCR relative to the MHC antigen-binding groove.

The crystal structure of the functional amino-terminal two-domain fragment of human vascular cell adhesion molecule 1 (VCAM-1) has been determined at 1.9 A resolution. The crystals contain two copies of the molecule in the asymmetric unit. The structure was solved by multiple isomorphous replacement, using lead and selenium derivatives. Anomalous scattering had to be used to resolve the phase ambiguity of a lead derivative. Since the selenium derivative has very small isomorphous differences, the local scaling algorithm had to be used to obtain an interpretable difference Patterson map. The initial phases were improved by non-crystallographic averaging, solvent flattening and histogram matching. The structure has been refined to a crystallographic R factor of 20.4% (15-1.9 A, F>/= 3sigma) and consists of two Ig domains (D1 and D2). The angle between these domains differs by 12 degrees between the two copies of the molecule in the crystallographic asymmetric unit, demonstrating that some movement is possible at the interface. In the amino-terminal domain D1 there is an 'extra' disulfide bond, in addition to the conserved cross-sheet disulfide bond, at the top of the molecule. This bond, a hallmark of the integrin-binding subclass of Ig superfamily proteins, makes the top of this domain very compact. The feature that projects most prominently from D1 is the CD loop, near the base of the domain. The key residue for integrin binding, Asp40, is located in this loop and is easily accessible.