NMR: an essential structural tool for integrative studies of T cell development, pMHC ligand recognition and TCR mechanobiology.

Journal of Biomolecular NMR
Robert J MallisEllis L Reinherz

Abstract

Early studies of T cell structural biology using X-ray crystallography, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) focused on a picture of the αβT cell receptor (αβTCR) component domains and their cognate ligands (peptides bound to MHC molecules, i.e. pMHCs) as static interaction partners. Moving forward requires integrating this corpus of data with dynamic technologies such as NMR, molecular dynamics (MD) simulations and real-time single molecule (SM) studies exemplified by optical tweezers (OT). NMR bridges relevant timescales and provides the potential for an all-atom dynamic description of αβTCR components prior to and during interactions with binding partners. SM techniques have opened up vistas in understanding the non-equilibrium nature of T cell signaling through the introduction of force-mediated binding measurements into the paradigm for T cell function. In this regard, bioforces consequent to T-lineage cell motility are now perceived as placing piconewton (pN)-level loads on single receptor-pMHC bonds to impact structural change and αβT-lineage biology, including peptide discrimination, cellular activation, and developmental progression. We discuss herein essential NMR technologies in ...Continue Reading

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Citations

Jul 18, 2019·Journal of Biomolecular NMR·Rob Kaptein, Gerhard Wagner
Dec 19, 2019·The Journal of Biological Chemistry·Roy A MariuzzaJohn Orban
Sep 26, 2019·Nature·Ellis L Reinherz
Aug 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wonmuk HwangEllis L Reinherz
Nov 30, 2019·Progress in Nuclear Magnetic Resonance Spectroscopy·Kai Klöpfer, Franz Hagn
Nov 5, 2020·Nature Communications·Soumya P BeheraHaribabu Arthanari

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