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9puk

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Neutralizing monoclonal antibody Fab fragment for human leptin

Structural highlights

9puk is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

Leptin as a key driver for organ fibrogenesis.,Sun XN, Chen S, Zhao S, Funcke JB, Virostek M, Pedersen L, Li C, Joung C, Lin Q, Li Y, Cobb A, Wang MY, Min K, Maya-Ramos L, Degasperi G, Liu J, Zhang N, An Z, Tomchick DR, Wynn RM, Oh DY, Scherer PE Sci Adv. 2025 Oct 24;11(43):eady7904. doi: 10.1126/sciadv.ady7904. Epub 2025 Oct , 22. PMID:41124259^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sun XN, Chen S, Zhao S, Funcke JB, Virostek M, Pedersen L, Li C, Joung C, Lin Q, Li Y, Cobb A, Wang MY, Min K, Maya-Ramos L, Degasperi G, Liu J, Zhang N, An Z, Tomchick DR, Wynn RM, Oh DY, Scherer PE. Leptin as a key driver for organ fibrogenesis. Sci Adv. 2025 Oct 24;11(43):eady7904. PMID:41124259 doi:10.1126/sciadv.ady7904