9PUO

Neutralizing monoclonal antibody Fab fragment bound to leptin

9PUO の概要

• エントリーDOI: 10.2210/pdb9puo/pdb
• 分子名称: Neutralizing antibody Fab fragment, heavy chain, Neutralizing antibody Fab fragment, light chain, Leptin, ... (4 entities in total)
• 機能のキーワード: antibody, fab, leptin, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 125388.29

構造登録者

Tomchick, D.R.,Wynn, R.M.,Scherer, P.E. (登録日: 2025-07-31, 公開日: 2025-11-05)

主引用文献

Sun, X.N.,Chen, S.,Zhao, S.,Funcke, J.B.,Virostek, M.,Pedersen, L.,Li, C.,Joung, C.,Lin, Q.,Li, Y.,Cobb, A.,Wang, M.Y.,Min, K.,Maya-Ramos, L.,Degasperi, G.,Liu, J.,Zhang, N.,An, Z.,Tomchick, D.R.,Wynn, R.M.,Oh, D.Y.,Scherer, P.E.
Leptin as a key driver for organ fibrogenesis.
Sci Adv, 11:eady7904-eady7904, 2025

PubMed Abstract: Leptin, a hormone primarily secreted by adipocytes, regulates energy balance and systemic metabolism through its interaction with the leptin receptor (LEPR). Beyond these functions, leptin signaling has been implicated in the pathogenesis of tissue fibrosis. Here, we report the x-ray crystal structures of a leptin-neutralizing antibody (hLep3) in the unbound and leptin-bound states. The interaction of this antibody with leptin mimics the interaction of the LEPR with leptin, providing direct insights into the mechanism by which the antibody disrupts leptin signaling. We furthermore evaluate the therapeutic potential of neutralizing leptin with this antibody across distinct mouse models of fibrosis affecting the kidney, liver, lung, heart, and blood vessels. Leptin neutralization markedly inhibited fibrosis progression in all models. Mechanistically, suppression of leptin activity reduces pro-inflammatory and profibrotic processes, underscoring its therapeutic potential. These findings suggest that leptin signaling plays a vital role in tissue fibrosis and that treatment with a leptin-neutralizing antibody may be a promising therapeutic approach.

PubMed: 41124259
DOI: 10.1126/sciadv.ady7904

実験手法

X-RAY DIFFRACTION (3.1 Å)