Structural highlights
Disease
LEP_HUMAN Defects in LEP may be a cause of obesity (OBESITY) [MIM:601665. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.[1]
Function
LEP_HUMAN May function as part of a signaling pathway that acts to regulate the size of the body fat depot. An increase in the level of LEP may act directly or indirectly on the CNS to inhibit food intake and/or regulate energy expenditure as part of a homeostatic mechanism to maintain constancy of the adipose mass.
Publication Abstract from PubMed
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.
The solution structure of human leptin reveals a conformational plasticity important for receptor recognition.,Fan X, Qin R, Yuan W, Fan JS, Huang W, Lin Z Structure. 2024 Jan 4;32(1):18-23.e2. doi: 10.1016/j.str.2023.10.009. Epub 2023 , Nov 3. PMID:37924810[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet. 1998 Mar;18(3):213-5. PMID:9500540 doi:10.1038/ng0398-213
- ↑ Fan X, Qin R, Yuan W, Fan JS, Huang W, Lin Z. The solution structure of human leptin reveals a conformational plasticity important for receptor recognition. Structure. 2024 Jan 4;32(1):18-23.e2. PMID:37924810 doi:10.1016/j.str.2023.10.009
