4RSU

Crystal structure of the light and hvem complex

Summary for 4RSU

• Entry DOI: 10.2210/pdb4rsu/pdb
• Related: 2AW2 4FHQ 4J6G
• Descriptor: Tumor necrosis factor ligand superfamily member 14, soluble form, Tumor necrosis factor receptor superfamily member 14, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: structural genomics, psi-biology, new york structural genomics, research consortium, nysgrc, immunity, n-glycosylation, membrane, secreted protein, cytokine, ifn, jelly-roll fold, protein structure initiative, atoms-to-animals: the immune function network, cysteine rich domain, signaling, cell membrane, secreted, immune system, new york structural genomics research consortium
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 197463.48

Authors

Liu, W.,Ramagoal, U.A.,Himmel, D.,Bonanno, J.B.,Nathenson, S.G.,Almo, S.C.,Atoms-to-Animals: The Immune Function Network (IFN),New York Structural Genomics Research Consortium (NYSGRC) (deposition date: 2014-11-11, release date: 2015-02-04, Last modification date: 2023-09-20)

Primary citation

Liu, W.,Chou, T.F.,Garrett-Thomson, S.C.,Seo, G.Y.,Fedorov, E.,Ramagopal, U.A.,Bonanno, J.B.,Wang, Q.,Kim, K.,Garforth, S.J.,Kakugawa, K.,Cheroutre, H.,Kronenberg, M.,Almo, S.C.
HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.
J.Exp.Med., 218:-, 2021

PubMed Abstract: HVEM is a TNF (tumor necrosis factor) receptor contributing to a broad range of immune functions involving diverse cell types. It interacts with a TNF ligand, LIGHT, and immunoglobulin (Ig) superfamily members BTLA and CD160. Assessing the functional impact of HVEM binding to specific ligands in different settings has been complicated by the multiple interactions of HVEM and HVEM binding partners. To dissect the molecular basis for multiple functions, we determined crystal structures that reveal the distinct HVEM surfaces that engage LIGHT or BTLA/CD160, including the human HVEM-LIGHT-CD160 ternary complex, with HVEM interacting simultaneously with both binding partners. Based on these structures, we generated mouse HVEM mutants that selectively recognized either the TNF or Ig ligands in vitro. Knockin mice expressing these muteins maintain expression of all the proteins in the HVEM network, yet they demonstrate selective functions for LIGHT in the clearance of bacteria in the intestine and for the Ig ligands in the amelioration of liver inflammation.

PubMed: 34709351
DOI: 10.1084/jem.20211112

Experimental method

X-RAY DIFFRACTION (2.3 Å)