The solution structure of human leptin reveals a conformational plasticity important for receptor recognition.
| Autor: | Fan X; School of Life Sciences, Tianjin University, Tianjin 300072, China., Qin R; School of Life Sciences, Tianjin University, Tianjin 300072, China., Yuan W; School of Life Sciences, Tianjin University, Tianjin 300072, China., Fan JS; Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA., Huang W; Department of Biochemistry and Molecular Biology, School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China. Electronic address: weidong1969@hotmail.com., Lin Z; School of Life Sciences, Tianjin University, Tianjin 300072, China. Electronic address: linzhi@linzhi.net. |
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| Jazyk: | angličtina |
| Zdroj: | Structure (London, England : 1993) [Structure] 2024 Jan 04; Vol. 32 (1), pp. 18-23.e2. Date of Electronic Publication: 2023 Nov 03. |
| DOI: | 10.1016/j.str.2023.10.009 |
| Abstrakt: | Leptin is a multi-potency cytokine that regulates various physiological functions, including weight control and energy homeostasis. Signaling of leptin is also important in many aging-related diseases. Leptin is required for the noncovalent crosslinking of different extracellular domains of leptin receptors, which is critical for receptor activation and downstream signaling. Nevertheless, the structure of intact apo-form leptin and the structural transition leptin undergoes upon receptor binding are not fully understood yet. Here, we determined the monomeric structure of wild-type human leptin by solution-state nuclear magnetic resonance spectroscopy. Leptin contains an intrinsically disordered region (IDR) in the internal A-B loop and the flexible helix E in the C-D loop, both of which undergo substantial local structural changes when leptin binds to its receptor. Our findings provide further insights into the molecular mechanisms of leptin signaling. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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