1XAU

STRUCTURE OF THE BTLA ECTODOMAIN

Summary for 1XAU

• Entry DOI: 10.2210/pdb1xau/pdb
• Descriptor: B- and T-lymphocyte attenuator, CADMIUM ION (3 entities in total)
• Functional Keywords: ig domain, beta sandwich, structural genomics, psi, protein structure initiative, midwest center for structural genomics, mcsg, immune system
• Biological source: Mus musculus (house mouse)
• Cellular location: Membrane; Single-pass type I membrane protein (Potential): Q7TSA3
• Total number of polymer chains: 1
• Total formula weight: 14372.72

Authors

Nelson, C.A.,Fremont, D.H.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2004-08-26, release date: 2004-10-05, Last modification date: 2024-10-09)

Primary citation

Nelson, C.A.,Fremont, M.D.,Sedy, J.R.,Norris, P.S.,Ware, C.F.,Murphy, K.M.,Fremont, D.H.
Structural determinants of herpesvirus entry mediator recognition by murine B and T lymphocyte attenuator.
J.Immunol., 180:940-947, 2008

PubMed Abstract: The B and T lymphocyte attenuator (BTLA) appears to act as a negative regulator of T cell activation and growth. BTLA specifically interacts with herpesvirus entry mediator (HVEM), a member of the TNFR family. Herein, we have undertaken surface plasmon resonance studies to quantitatively assess BTLA and HVEM ectodomain interactions. We find that soluble BALB/cJ BTLA engages HVEM with an equilibrium affinity of 0.97+/-0.19 microM while the C57BL/6 BTLA binds slightly better with an equilibrium affinity of 0.42+/-0.06 microM. Despite its lower affinity for HVEM, the kinetic half-life of BALB/cJ BTLA complexes are twice as long as observed for C57BL/6 BTLA (4 vs 2 s). To further explore these interactions, we solved the crystal structure of a murine BTLA (BALB/cJ) ectodomain at 1.8-A resolution, revealing a beta sandwich fold with strong similarity to I-set members of the Ig superfamily. Using a structure-based mutagenesis strategy, we then examined the individual contributions of 26 BTLA surface-exposed residues toward HVEM binding. Four single-site substitutions were identified that decrease HVEM binding below detectable levels and two that decrease binding by more than half. All six of these cluster at the edge of the beta sandwich in a membrane distal patch formed primarily from the A and G strands. This patch falls within the contacting surface recently revealed in the crystal structure of the human BTLA-HVEM cocomplex. The critical binding residues identified here are highly conserved across species, suggesting that BTLA employs a conserved binding mode for HVEM recognition.

PubMed: 18178834

Experimental method

X-RAY DIFFRACTION (1.8 Å)