1xau Citations

Structural determinants of herpesvirus entry mediator recognition by murine B and T lymphocyte attenuator.

J Immunol 180 940-7 (2008)
Cited: 29 times
EuropePMC logo PMID: 18178834

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.

Articles - 1xau mentioned but not cited (4)

  1. Towards fully automated structure-based function prediction in structural genomics: a case study. Watson JD, Sanderson S, Ezersky A, Savchenko A, Edwards A, Orengo C, Joachimiak A, Laskowski RA, Thornton JM. J Mol Biol 367 1511-1522 (2007)
  2. Detecting protein candidate fragments using a structural alphabet profile comparison approach. Shen Y, Picord G, Guyon F, Tuffery P. PLoS One 8 e80493 (2013)
  3. Structure of human cytomegalovirus UL144, an HVEM orthologue, bound to the B and T cell lymphocyte attenuator. Bitra A, Nemčovičová I, Picarda G, Doukov T, Wang J, Benedict CA, Zajonc DM. J Biol Chem 294 10519-10529 (2019)
  4. Statistical dictionaries for hypothetical in silico model of the early-stage intermediate in protein folding. Kalinowska B, Fabian P, Stąpor K, Roterman I. J Comput Aided Mol Des 29 609-618 (2015)


Reviews citing this publication (11)

  1. The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation. Cai G, Freeman GJ. Immunol Rev 229 244-258 (2009)
  2. Slow down and survive: Enigmatic immunoregulation by BTLA and HVEM. Murphy TL, Murphy KM. Annu Rev Immunol 28 389-411 (2010)
  3. The signaling networks of the herpesvirus entry mediator (TNFRSF14) in immune regulation. Steinberg MW, Cheung TC, Ware CF. Immunol Rev 244 169-187 (2011)
  4. HVEM/LIGHT/BTLA/CD160 cosignaling pathways as targets for immune regulation. del Rio ML, Lucas CL, Buhler L, Rayat G, Rodriguez-Barbosa JI. J Leukoc Biol 87 223-235 (2010)
  5. Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections. Pentcheva-Hoang T, Corse E, Allison JP. Immunol Rev 229 67-87 (2009)
  6. Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways. Ware CF. Immunol Rev 223 186-201 (2008)
  7. Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'. Rich RL, Myszka DG. J Mol Recognit 23 1-64 (2010)
  8. Cross-regulation between herpesviruses and the TNF superfamily members. Sedý JR, Spear PG, Ware CF. Nat Rev Immunol 8 861-873 (2008)
  9. PD-1/PD-L1, PD-1/PD-L2, and other co-inhibitory signaling pathways in transplantation. del Rio ML, Buhler L, Gibbons C, Tian J, Rodriguez-Barbosa JI. Transpl Int 21 1015-1028 (2008)
  10. Regulating the mucosal immune system: the contrasting roles of LIGHT, HVEM, and their various partners. Steinberg MW, Shui JW, Ware CF, Kronenberg M. Semin Immunopathol 31 207-221 (2009)
  11. The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis. De Trez C, Ware CF. Cytokine Growth Factor Rev 19 277-284 (2008)

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