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Advances in Structure Determination of G Protein-Coupled Receptors by SFX

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X-ray Free Electron Lasers

Abstract

G protein-coupled receptors (GPCRs) constitute the largest superfamily of membrane proteins, members of which are involved in regulation of critical sensory and physiological processes in the human body. High-resolution GPCR structures are essential for the elucidation of the molecular mechanisms of signal transduction, and for the rational design of more effective therapeutics. GPCR structure determination is, however, hampered by challenges in their expression, stabilization, and crystallization. The recent emergence of X-ray free electron lasers (FELs), and establishment of serial femtosecond crystallography (SFX) have advanced the field of structural biology by enabling access to high-resolution structure and dynamics of challenging to crystallize and radiation damage-sensitive macromolecules. In this chapter we outline relevant SFX technology developments and its applications to structural studies of GPCRs, shedding light on ligand binding to antitumor and anti-addiction targets, uncovering molecular mechanisms behind distinct functions of angiotensin receptors, elucidating full-length structures of multidomain class B and Frizzled receptors, and revealing details of interactions between GPCRs and arrestins.

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Authors and Affiliations

  1. Department of Chemistry, Bridge Institute, University of Southern California, Los Angeles, CA, USA

    Benjamin Stauch, Linda Johansson, Andrii Ishchenko, Gye Won Han & Vadim Cherezov

  2. Linac Coherent Light Source, Stanford Linear Accelerator Center (SLAC) National Accelerator Laboratory, Menlo Park, CA, USA

    Alexander Batyuk

Authors
  1. Benjamin Stauch
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  2. Linda Johansson
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  3. Andrii Ishchenko
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  4. Gye Won Han
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  5. Alexander Batyuk
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  6. Vadim Cherezov
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Corresponding author

Correspondence to Vadim Cherezov .

Editor information

Editors and Affiliations

  1. SLAC National Accelerator Laboratory, Menlo Park, CA, USA

    Sébastien Boutet

  2. School of Molecular Sciences, Arizona State University, Tempe, AZ, USA

    Petra Fromme

  3. SLAC National Accelerator Laboratory, Menlo Park, CA, USA

    Mark S. Hunter

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Stauch, B., Johansson, L., Ishchenko, A., Han, G.W., Batyuk, A., Cherezov, V. (2018). Advances in Structure Determination of G Protein-Coupled Receptors by SFX. In: Boutet, S., Fromme, P., Hunter, M. (eds) X-ray Free Electron Lasers. Springer, Cham. https://doi.org/10.1007/978-3-030-00551-1_10

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