9VOR

Cryo-EM Structure of Human GPR158 Bound to Nanobody Nb20

9VOR の概要

• エントリーDOI: 10.2210/pdb9vor/pdb
• EMDBエントリー: 65225
• 分子名称: Metabotropic glycine receptor, Nb20, CHOLESTEROL, ... (5 entities in total)
• 機能のキーワード: gpcr, orphan receptor, nanobody, rgs proteins, signalling receptor, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 219261.38

構造登録者

Laboute, T.,Zucca, S.,Sial, M.,Sharma, M.,Brunori, G.,Singh, S.,Singh, A.,Martemyanov, K. (登録日: 2025-07-02, 公開日: 2025-12-31, 最終更新日: 2026-02-18)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.47 Å)