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 SOSUIBUMBBELL
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 calciumbinding
protein, showing that this form is mainly governed by short-range
interactions.
