Cited by 234Receptor Mechanisms and SignalingEnzyme Structure and FunctionProtein Structure and Dynamics

Nanobody stabilization of G protein-coupled receptor conformational states

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Steyaert, Jan, Kobilka, Brian K·2011·Current Opinion in Structural Biology

Abstract

Remarkable progress has been made in the field of G protein-coupled receptor (GPCR) structural biology during the past four years. Several obstacles to generating diffraction quality crystals of GPCRs have been overcome by combining innovative methods ranging from protein engineering to lipid-based screens and microdiffraction technology. The initial GPCR structures represent energetically stable inactive-state conformations. However, GPCRs signal through different G protein isoforms or G protein-independent effectors upon ligand binding suggesting the existence of multiple ligand-specific active states. These active-state conformations are unstable in the absence of specific cytosolic signaling partners representing new challenges for structural biology. Camelid single chain antibody fragments (nanobodies) show promise for stabilizing active GPCR conformations and as chaperones for crystallogenesis.

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Crossref · 10.1016/j.sbi.2011.06.011

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  • The absence of the L chain means that nanobody CDRs are distinct from those of antibodies in both sequence and structure, and as a result nanobodies are able to bind antibody-inaccessible epitopes in enzyme active sites, viral capsids and G protein coupled receptors.

    “The absence of the L chain means that the nanobody’s CDRs are distinct from those of antibodies in both sequence and structure, and as a result nanobodies are able to bind antibody-inaccessible epitopes in enzyme active sites, viral capsids and G protein coupled receptors [233, 234].”

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Authors
Steyaert, J., & Kobilka, B. K.
Affiliations
  • Vrije Universiteit Brussel (BE)
  • Stanford Medicine (US)
Corresponding author
Steyaert, Jan
Venue
Current Opinion in Structural Biology
Publisher
Elsevier BV
Published
2011-08
Volume
21
Issue
4
Pages
567-572
ISSN
0959-440X (ISSN-L)
OpenAlex
W1975641514
Cited by
234
References
50
Citations by year
2026: 5 · 2025: 13 · 2024: 10 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 14 · 2019: 21 · 2018: 17 · 2017: 21 · 2016: 15 · 2015: 18 · 2014: 30 · 2013: 36 · 2012: 9
FWCI
2.21
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Structural Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
  • National Institute of General Medical Sciences (GM083118, R01GM083118)
  • National Institute of Neurological Disorders and Stroke (NS-028471, R01NS028471, R37NS028471)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
G protein-coupled receptors, nanobodies, G protein-independent signaling, crystallogenesis, molecular chaperones
MeSH terms
Animals, Humans, Immunoglobulin Fragments, Protein Conformation, Crystallography, X-Ray, Receptors, G-Protein-Coupled, Protein Stability, Single-Chain Antibodies

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