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An investigation into the relationship between calmodulin protein conformation and binding specificity
Author(s) -
Dunlap Tori,
Bradley Luke H.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.863.3
Subject(s) - calmodulin , linker , calcium binding protein , circular dichroism , biophysics , chemistry , conformational change , binding site , binding protein , binding domain , plasma protein binding , biochemistry , calcium , stereochemistry , biology , enzyme , organic chemistry , computer science , gene , operating system
In the presence of calcium, calmodulin (CaM) undergoes large conformational changes throughout the protein to present a structurally dynamic surface that can recognize and bind numerous target proteins to transduce the cell's calcium signal. Most of these structural changes occur in the protein's unique central linker region, which serves as a molecular hinge between the N‐ and C‐terminal dual EF‐hand calcium binding domains. Numerous studies have led to the hypothesis that the interactions provided by this region are primarily responsible for CaM‐target binding affinity and thus, CaM's binding specificity. To further examine the relationship between protein sequence, conformation, and CaM's pluripotent binding specificity, we constructed linker‐region protein libraries designed to differentially restrict the conformational freedom of the molecule. Individual, non‐selected library members were characterized by circular dichroism spectroscopy to investigate alterations in conformational change upon calcium binding, and fluorescence binding studies with CaM‐peptide targets to investigate changes in binding specificity. We present the initial structural and binding characterization of these randomly selected library proteins.