9VOR

Cryo-EM Structure of Human GPR158 Bound to Nanobody Nb20

Summary for 9VOR

• Entry DOI: 10.2210/pdb9vor/pdb
• EMDB information: 65225
• Descriptor: Metabotropic glycine receptor, Nb20, CHOLESTEROL, ... (5 entities in total)
• Functional Keywords: gpcr, orphan receptor, nanobody, rgs proteins, signalling receptor, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 219261.38

Authors

Laboute, T.,Zucca, S.,Sial, M.,Sharma, M.,Brunori, G.,Singh, S.,Singh, A.,Martemyanov, K. (deposition date: 2025-07-02, release date: 2025-12-31, Last modification date: 2026-02-18)

Primary citation

Laboute, T.,Zucca, S.,Sial, O.K.,Sharma, M.,Brunori, G.,Singh, S.,Nageswar, K.V.,Peng, H.,Rader, C.,Becker, J.A.,Le Merrer, J.,Singh, A.K.,Martemyanov, K.A.
Targeting mGlyR with nanobodies for depression.
Nat Commun, 17:831-831, 2026

PubMed Abstract: Development of therapies for neuropsychiatric conditions is one of the greatest challenges of modern medicine. Common limitations of traditional small molecule drugs include poor efficacy, off-target side effects and difficult druggability of many targets. In this study, we report a different approach deploying small engineered single domain antibodies, known as nanobodies, for the treatment of depression, a prevalent neuropsychiatric condition. We develop highly selective nanobodies for a recently discovered glycine receptor mGlyR crucially linked to pathophysiology of depression. Using a mouse model of stress-induced depression, we show that non-invasive intranasal delivery of nanobody produces rapid and lasting anti-depressant effect. We solve an atomic structure of mGlyR bound to nanobody and use a variety of cell-based approaches to reveal the mechanism of mGlyR modulation and its impact on neural circuitry. These findings support development of biologics for the treatment of intractable brain disorders.

PubMed: 41588006
DOI: 10.1038/s41467-026-68339-x

Experimental method

ELECTRON MICROSCOPY (3.47 Å)