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NMR structure of water-soluble domain of human Lynx2 (Lypd1) protein
Structural highlights
Publication Abstract from PubMedLy-6/uPAR or three-finger proteins (TFPs) contain a disulfide-stabilized beta-structural core and three protruding loops (fingers). In mammals, TFPs have been found in epithelium and the nervous, endocrine, reproductive, and immune systems. Here, using heteronuclear NMR, we determined the three-dimensional (3D) structure and backbone dynamics of the epithelial secreted protein SLURP-1 and soluble domains of GPI-anchored TFPs from the brain (Lynx2, Lypd6, Lypd6b) acting on nicotinic acetylcholine receptors (nAChRs). Results were compared with the data about human TFPs Lynx1 and SLURP-2 and snake alpha-neurotoxins WTX and NTII. Two different topologies of the beta-structure were revealed: one large antiparallel beta-sheet in Lypd6 and Lypd6b, and two beta-sheets in other proteins. alpha-Helical segments were found in the loops I/III of Lynx2, Lypd6, and Lypd6b. Differences in the surface distribution of charged and hydrophobic groups indicated significant differences in a mode of TFPs/nAChR interactions. TFPs showed significant conformational plasticity: the loops were highly mobile at picosecond-nanosecond timescale, while the beta-structural regions demonstrated microsecond-millisecond motions. SLURP-1 had the largest plasticity and characterized by the unordered loops II/III and cis-trans isomerization of the Tyr39-Pro40 bond. In conclusion, plasticity could be an important feature of TFPs adapting their structures for optimal interaction with the different conformational states of nAChRs. Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors.,Paramonov AS, Kocharovskaya MV, Tsarev AV, Kulbatskii DS, Loktyushov EV, Shulepko MA, Kirpichnikov MP, Lyukmanova EN, Shenkarev ZO Int J Mol Sci. 2020 Oct 1;21(19). pii: ijms21197280. doi: 10.3390/ijms21197280. PMID:33019770[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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