Sequence, structure, function, immunity: Structural genomics of costimulation

Kausik Chattopadhyay, Eszter Lazar-Molnar, Qingrong Yan, Rotem Rubinstein, Chenyang Zhan, Vladimir Vigdorovich, Udupi A. Ramagopal, Jeffrey Bonanno, Stanley G. Nathenson, Steven C. Almo

Research output: Contribution to journalReview article

59 Scopus citations

Abstract

Costimulatory receptors and ligands trigger the signaling pathways that are responsible for modulating the strength, course, and duration of an immune response. High-resolution structures have provided invaluable mechanistic insights by defining the chemical and physical features underlying costimulatory receptor:ligand specificity, affinity, oligomeric state, and valency. Furthermore, these structures revealed general architectural features that are important for the integration of these interactions and their associated signaling pathways into overall cellular physiology. Recent technological advances in structural biology promise unprecedented opportunities for furthering our understanding of the structural features and mechanisms that govern costimulation. In this review, we highlight unique insights that have been revealed by structures of costimulatory molecules from the immunoglobulin and tumor necrosis factor superfamilies and describe a vision for future structural and mechanistic analysis of costimulation. This vision includes simple strategies for the selection of candidate molecules for structure determination and highlights the critical role of structure in the design of mutant costimulatory molecules for the generation of in vivo structure-function correlations in a mammalian model system. This integrated 'atoms-to-animals' paradigm provides a comprehensive approach for defining atomic and molecular mechanisms.

Original languageEnglish (US)
Pages (from-to)356-386
Number of pages31
JournalImmunological Reviews
Volume229
Issue number1
DOIs
StatePublished - May 2009

Keywords

  • Immunoglobulin superfamily
  • Structure
  • T-cell costimulation
  • TNF/TNFR superfamily

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chattopadhyay, K., Lazar-Molnar, E., Yan, Q., Rubinstein, R., Zhan, C., Vigdorovich, V., Ramagopal, U. A., Bonanno, J., Nathenson, S. G., & Almo, S. C. (2009). Sequence, structure, function, immunity: Structural genomics of costimulation. Immunological Reviews, 229(1), 356-386. https://doi.org/10.1111/j.1600-065X.2009.00778.x