6U6V

Crystal structure of human PD-1H / VISTA

Summary for 6U6V

• Entry DOI: 10.2210/pdb6u6v/pdb
• Descriptor: V-type immunoglobulin domain-containing suppressor of T-cell activation, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: t cell co-inhibition, immunoglobulin-like, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 19900.18

Authors

Slater, B.T.,Han, X.,Chen, L.,Xiong, Y. (deposition date: 2019-08-30, release date: 2020-01-01, Last modification date: 2024-10-16)

Primary citation

Slater, B.T.,Han, X.,Chen, L.,Xiong, Y.
Structural insight into T cell coinhibition by PD-1H (VISTA).
Proc.Natl.Acad.Sci.USA, 117:1648-1657, 2020

PubMed Abstract: Programmed death-1 homolog (PD-1H), a CD28/B7 family molecule, coinhibits T cell activation and is an attractive immunotherapeutic target for cancer and inflammatory diseases. The molecular basis of its function, however, is unknown. Bioinformatic analyses indicated that PD-1H has a very long Ig variable region (IgV)-like domain and extraordinarily high histidine content, suggesting that unique structural features may contribute to coinhibitory mechanisms. Here we present the 1.9-Å crystal structure of the human PD-1H extracellular domain. It reveals an elongated CC' loop and a striking concentration of histidine residues, located in the complementarity-determining region-like proximal half of the molecule. We show that surface-exposed histidine clusters are essential for robust inhibition of T cell activation. PD-1H exhibits a noncanonical IgV-like topology including an extra "H" β-strand and "clamping" disulfide, absent in known IgV-like structures, that likely restricts its orientation on the cell surface differently from other IgV-like domains. These results provide important insight into a molecular basis of T cell coinhibition by PD-1H.

PubMed: 31919279
DOI: 10.1073/pnas.1908711117

Experimental method

X-RAY DIFFRACTION (1.9 Å)