What determines the degree of compactness of a calcium-binding protein?
The EF-hand calcium-binding proteins may exist either in an extended or a compact conformation. This conformation is sometimes correlated with the function of the calcium-binding protein. For those proteins whose structure and function are known, calcium sensors are usually extended and calcium buffers compact; hence, there is interest in predicting the form of the protein starting from its sequence. In the present study, we used two different procedures: one that already exists in the literature, the sosuidumbbell algorithm, mainly based on the charges of the two EF-hand domains, and the other comprising a novel procedure that is based on linker average hydrophilicity. The linker consists of the residues that connect the domains. The two procedures were tested on 17 known-structure calcium-binding proteins and then applied to 59 unknown-structure centrins. The sosuidumbbell algorithm yielded the correct conformations for only 15 of the known-structure proteins and predicted that all centrins should be in a closed form. The linker average hydrophilicity procedure discriminated well between all the extended and non-extended forms of the known-structure calcium-binding proteins, and its prediction concerning centrins reflected well their phylogenetic classification. The linker average hydrophilicity criterion is a simple and powerful means to discriminate between extended and non-extended forms of calcium-binding proteins. What is remarkable is that only a few residues that constitute the linker (between 2 and 20 in our tested sample of proteins) are responsible for the form of the calcium-binding protein, showing that this form is mainly governed by short-range interactions.
Mouawad
Liliane
L
Inserm U759/Institut Curie-Recherche, Centre Universitaire Paris-Sud, Orsay, France. liliane.mouawad@curie.u-psud.fr
Isvoran
Adriana
A
Quiniou
Eric
E
Craescu
Constantin T
CT
D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D020832:EF Hand Motifs / Q000502:physiology*; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation
D002135:Calcium-Binding Proteins