8h0g | pdb_00008h0g
AQEE-30 in a HFIP solution
Structural highlights
FunctionVGF_HUMAN Secreted polyprotein that is packaged and proteolytically processed by prohormone convertases PCSK1 and PCSK2 in a cell-type-specific manner (By similarity). VGF and peptides derived from its processing play many roles in neurogenesis and neuroplasticity associated with learning, memory, depression and chronic pain (By similarity).[UniProtKB:P20156][UniProtKB:Q0VGU4] Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Suppresses presynaptic glutamatergic neurons connected to vasopressin neurons.[UniProtKB:P20156] Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Activates GABAergic interneurons which are inhibitory neurons of the nervous system and thereby suppresses presynaptic glutamatergic neurons (By similarity). Stimulates also feeding behavior in an orexin-dependent manner in the hypothalamus (By similarity). Functions as a positive regulator for the activation of orexin neurons resulting in elevated gastric acid secretion and gastric emptying (By similarity).[UniProtKB:P20156] Secreted multifunctional neuropeptide that binds to different cell receptors and thereby plays multiple physiological roles including modulation of energy expenditure, pain, response to stress, gastric regulation, glucose homeostasis as well as lipolysis (By similarity). Activates the G-protein-coupled receptor C3AR1 via a folding-upon-binding mechanism leading to enhanced lipolysis in adipocytes (By similarity). Interacts with C1QBP receptor in macrophages and microglia causing increased levels of intracellular calcium and hypersensitivity (By similarity).[UniProtKB:P20156][UniProtKB:Q0VGU4] Plays a role in the regulation of memory formation and depression-related behaviors potentially by influencing synaptic plasticity and neurogenesis. Induces acute and transient activation of the NTRK2/TRKB receptor and subsequent CREB phosphorylation (By similarity). Induces also insulin secretion in insulinoma cells by increasing intracellular calcium mobilization (By similarity).[UniProtKB:Q0VGU4] Has bactericidal activity against M. luteus, and antifungal activity against P. Pastoris.[1] Publication Abstract from PubMedAQEE-30 is one of the VGF peptides, which are derived from the VGF polypeptide precursor, and related to various physiological phenomena including neuroprotective effects in Huntington's disease and amyotrophic lateral sclerosis (ALS). Although various functions of AQEE-30 have been reported so far, the structure of this peptide has not been reported yet. In this study, the structure of human AQEE-30 was investigated in hexafluoroisopropanol (HFIP) and dodecyl phosphocholine (DPC) micelle solutions, using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. CD results showed that AQEE-30 had a partial helical structure in aqueous buffer, and the helical structure was stabilized in the HFIP and DPC micelle solutions. The 3D structures determined by NMR spectroscopy showed that AQEE-30 adopted mainly alpha-helical structure in both the HFIP and DPC micelle solutions. The surface of AQEE-30 showed that it was predominantly negatively charged. The residues from 601 to 611 in both the HFIP and DPC micelle solutions showed amphiphilicity with four negatively charged residues, glutamate. The C-terminal consecutive arginine residues formed a partial positively charged surface. These results suggest an alpha-helical active structure of AQEE-30 in the cell-membrane environment. Structure of AQEE-30 of VGF Neuropeptide in Membrane-Mimicking Environments.,Park OS, Bang JK, Cheong C, Jeon YH Int J Mol Sci. 2022 Nov 12;23(22):13953. doi: 10.3390/ijms232213953. PMID:36430431[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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