2L03

Spatial structure of water-soluble Lynx1

Summary for 2L03

• Entry DOI: 10.2210/pdb2l03/pdb
• Descriptor: Ly-6/neurotoxin-like protein 1 (1 entity in total)
• Functional Keywords: lynx1, acetylcholine receptor, endogenic neuromodulator, three-finger toxins, neuropeptide
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Secreted (Potential). Isoform 2: Cell membrane; Lipid-anchor, GPI- anchor (Potential). Isoform 3: Secreted: Q9BZG9
• Total number of polymer chains: 1
• Total formula weight: 8418.71

Authors

Mineev, K.S.,Shenkarev, Z.O.,Arseniev, A.S. (deposition date: 2010-06-30, release date: 2011-01-19, Last modification date: 2014-10-01)

Primary citation

Lyukmanova, E.N.,Shenkarev, Z.O.,Shulepko, M.A.,Mineev, K.S.,D'Hoedt, D.,Kasheverov, I.E.,Filkin, S.Y.,Krivolapova, A.P.,Janickova, H.,Dolezal, V.,Dolgikh, D.A.,Arseniev, A.S.,Bertrand, D.,Tsetlin, V.I.,Kirpichnikov, M.P.
NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1
J.Biol.Chem., 286:10618-10627, 2011

PubMed Abstract: Discovery of proteins expressed in the central nervous system sharing the three-finger structure with snake α-neurotoxins provoked much interest to their role in brain functions. Prototoxin LYNX1, having homology both to Ly6 proteins and three-finger neurotoxins, is the first identified member of this family membrane-tethered by a GPI anchor, which considerably complicates in vitro studies. We report for the first time the NMR spatial structure for the water-soluble domain of human LYNX1 lacking a GPI anchor (ws-LYNX1) and its concentration-dependent activity on nicotinic acetylcholine receptors (nAChRs). At 5-30 μM, ws-LYNX1 competed with (125)I-α-bungarotoxin for binding to the acetylcholine-binding proteins (AChBPs) and to Torpedo nAChR. Exposure of Xenopus oocytes expressing α7 nAChRs to 1 μM ws-LYNX1 enhanced the response to acetylcholine, but no effect was detected on α4β2 and α3β2 nAChRs. Increasing ws-LYNX1 concentration to 10 μM caused a modest inhibition of these three nAChR subtypes. A common feature for ws-LYNX1 and LYNX1 is a decrease of nAChR sensitivity to high concentrations of acetylcholine. NMR and functional analysis both demonstrate that ws-LYNX1 is an appropriate model to shed light on the mechanism of LYNX1 action. Computer modeling, based on ws-LYNX1 NMR structure and AChBP x-ray structure, revealed a possible mode of ws-LYNX1 binding.

PubMed: 21252236
DOI: 10.1074/jbc.M110.189100

Experimental method

SOLUTION NMR