5T7C

Solution structure of calcium free, myristoylated visinin-like protein 3

Summary for 5T7C

• Entry DOI: 10.2210/pdb5t7c/pdb
• NMR Information: BMRB: 18627
• Descriptor: Hippocalcin-like protein 1 (1 entity in total)
• Functional Keywords: calmodulin, hippocalcin, neuronal calcium sensor, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 22421.36

Authors

Lim, S.,Ames, J.B. (deposition date: 2016-09-02, release date: 2017-07-12, Last modification date: 2023-06-14)

Primary citation

Li, C.,Lim, S.,Braunewell, K.H.,Ames, J.B.
Structure and Calcium Binding Properties of a Neuronal Calcium-Myristoyl Switch Protein, Visinin-Like Protein 3.
PLoS ONE, 11:e0165921-e0165921, 2016

PubMed Abstract: Visinin-like protein 3 (VILIP-3) belongs to a family of Ca2+-myristoyl switch proteins that regulate signal transduction in the brain and retina. Here we analyze Ca2+ binding, characterize Ca2+-induced conformational changes, and determine the NMR structure of myristoylated VILIP-3. Three Ca2+ bind cooperatively to VILIP-3 at EF2, EF3 and EF4 (KD = 0.52 μM and Hill slope of 1.8). NMR assignments, mutagenesis and structural analysis indicate that the covalently attached myristoyl group is solvent exposed in Ca2+-bound VILIP-3, whereas Ca2+-free VILIP-3 contains a sequestered myristoyl group that interacts with protein residues (E26, Y64, V68), which are distinct from myristate contacts seen in other Ca2+-myristoyl switch proteins. The myristoyl group in VILIP-3 forms an unusual L-shaped structure that places the C14 methyl group inside a shallow protein groove, in contrast to the much deeper myristoyl binding pockets observed for recoverin, NCS-1 and GCAP1. Thus, the myristoylated VILIP-3 protein structure determined in this study is quite different from those of other known myristoyl switch proteins (recoverin, NCS-1, and GCAP1). We propose that myristoylation serves to fine tune the three-dimensional structures of neuronal calcium sensor proteins as a means of generating functional diversity.

PubMed: 27820860
DOI: 10.1371/journal.pone.0165921

Experimental method

SOLUTION NMR