Nanobody stabilization of G protein-coupled receptor conformational states
Open accessAbstract
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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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].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [234]
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“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)
- PMC
- PMC3166880
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- 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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