Person:

Chen, Qian

The (\alpha\beta) T cell receptor (TCR) is a multimeric complex whose (\beta) chain plays a crucial role in thymocyte development as well as antigen recognition by mature T lymphocytes. We report here crystal structures of individual (\beta) subunits, termed N15(\beta) (V(\beta)5.2D(\beta)2J(\beta)2.6C(\beta)2) and N30(\beta) (V(\beta)13D(\beta)1J(\beta)1.1C(\beta)2), derived from two (\alpha\beta) TCRs specific for the immunodominant vesicular stomatitis virus octapeptide (VSV-8) bound to the murine H-2K(^b) MHC class I molecule. The crystal packing of the N15(\beta) structure reveals a homodimer formed through two V(\beta) domains. The V(\beta)/V(\beta) module is topologically very similar to the V(\alpha)/V(\beta) module in the N15(\alpha\beta) heterodimer. By contrast, in the N30(\beta) structure, the V(\beta) domain’s external hydrophobic CFG face is covered by the neighboring molecule’s C(\beta) domain. In conjunction with systematic investigation of previously published TCR single-subunit structures, we identified several conserved residues forming a concave hydrophobic patch at the center of the CFG outer face of the V(\beta) and other V-type Ig-like domains. This hydrophobic patch is shielded from solvent exposure in the crystal packing, implying that it is unlikely to be thermodynamically stable if exposed on the thymocyte surface. Accordingly, we propose a dimeric pre-TCR model distinct from those suggested previously by others and discuss its functional and structural implications.

Understanding structural details of colloidal nanoparticles is required to bridge our knowledge about their synthesis, growth mechanisms, and physical properties. We introduce a method for determining 3D structures of individual nanoparticles in solution. We combine a graphene liquid cell, high-resolution transmission electron microscopy, a direct electron detector, and an algorithm for single-particle 3D reconstruction originally developed for analysis of biological molecules to produce two near-atomic resolution 3D structures of individual Pt nanocrystals. Since our method derives the 3D structure from images of individual nanoparticles rotating freely in solution, it enables the analysis of heterogeneous populations of potentially unordered nanoparticles that are synthesized in solution, thereby providing a means to understand the structure and stability of defects at the nanoscale.