PDBsum entry 3cs1

Metal binding protein

PDB id: 3cs1

Contents

Protein chain

192 a.a.

Waters ×65

References listed in PDB file

Key reference

• Title: Structural insights into membrane targeting by the flagellar calcium-Binding protein (fcabp), A myristoylated and palmitoylated calcium sensor in trypanosoma cruzi.
• Authors: J.N.Wingard, J.Ladner, M.Vanarotti, A.J.Fisher, H.Robinson, K.T.Buchanan, D.M.Engman, J.B.Ames.
• Ref.: J Biol Chem, 2008, 283, 23388-23396.
• PubMed id: 18559337

Abstract

The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca(2+)-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca(2+)-free state determined at 2.2A resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically with flagellar membrane targets. The four EF-hands in FCaBP each adopt a "closed conformation" similar to that seen in Ca(2+)-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca(2+)-free and Ca(2+)-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca(2+)-induced conformational changes may control its binding to membrane-bound protein targets.