title: Divalent cations and redox conditions regulate the molecular structure and function of visinin-like protein-1.
abstract: The NCS protein Visinin-like Protein 1 (VILIP-1) transduces calcium signals in the brain and serves as an effector of the non-retinal receptor guanylyl cyclases (GCs) GC-A and GC-B, and nicotinic acetyl choline receptors (nAchR). Analysis of the quaternary structure of VILIP-1 in solution reveals the existence of monomeric and dimeric species, the relative contents of which are affected but not exclusively regulated by divalent metal ions and Redox conditions. Using small-angle X-ray scattering, we have investigated the low resolution structure of the calcium-bound VILIP-1 dimer under reducing conditions. Scattering profiles for samples with high monomeric and dimeric contents have been obtained. The dimerization interface involves residues from EF-hand regions EF3 and EF4.Using monolayer adsorption experiments, we show that myristoylated and unmyristoylated VILIP-1 can bind lipid membranes. The presence of calcium only marginally improves binding of the protein to the monolayer, suggesting that charged residues at the protein surface may play a role in the binding process.In the presence of calcium, VILIP-1 undergoes a conformational re-arrangement, exposing previously hidden surfaces for interaction with protein partners. We hypothesise a working model where dimeric VILIP-1 interacts with the membrane where it binds membrane-bound receptors in a calcium-dependent manner.
authors.affiliation: Structural Chemistry Program, Eskitis Institute for Cell & Molecular Therapies, Griffith University, Brisbane, Queensland, Australia. conan.wang@griffith.edu.au
authors.forename: Conan K
authors.initials: CK
authors.lastname: Wang
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Christian M
authors.initials: CM
authors.lastname: Jessen
authors.forename: Cristiano L P
authors.initials: CL
authors.lastname: Oliveira
authors.forename: Lynsey
authors.initials: L
authors.lastname: Mack
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Braunewell
authors.forename: James B
authors.initials: JB
authors.lastname: Ames
authors.forename: Jan Skov
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
mesh_terms: D000595:Amino Acid Sequence; D002413:Cations, Divalent; D002460:Cell Line; D002850:Chromatography, Gel; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051596:Neurocalcin / Q000737:chemistry* / Q000502:physiology*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002413:Cations, Divalent; D051596:Neurocalcin
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