Divalent Cations and Redox Conditions Regulate the Molecular Structure and Function of Visinin-Like Protein-1 Author

The NCS protein Visinin-like Protein 1 (VILIP-1) transduces calcium signals in the brain and serves as an effector of the nonretinal 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. Citation: Wang CK, Simon A, Jessen CM, Oliveira CLP, Mack L, et al. (2011) Divalent Cations and Redox Conditions Regulate the Molecular Structure and Function of Visinin-Like Protein-1. PLoS ONE 6(11): e26793. doi:10.1371/journal.pone.0026793 Editor: Bostjan Kobe, University of Queensland, Australia Received August 5, 2011; Accepted October 4, 2011; Published November 2, 2011 Copyright: 2011 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported in parts by Fundaçao Bial, the Rebecca Cooper Foundation (AH), and National Institutes of Health (grant EY012347, J.B.A.). C.W. is supported by an National Health and Medical Research Council postdoctoral training fellowship (37677). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]