Deriving how far structural information is transmitted through parallel homodimeric coiled-coils: A correlation analysis of helical staggers


  • Jerry H. Brown

    Corresponding author
    1. Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454-9110
    • Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454-9110
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How local conformation is affected by local sequence is fairly well understood for alpha-helical coiled-coils, but less is known about how local conformation is influenced by distant features. Here, I describe an approach to detect such an effect, based on computing correlation coefficients of local out-of-register alignments, or so-called “staggers” between the helices, as a function of the axial distance between the staggers. This approach requires parallel homodimers, in which each stagger can occur with two “signs,” where either one helix or the other is shifted towards the N terminus. The signs of such staggers separated by up to 12 residues are strongly correlated, indicating that the conformations of the ends of coiled-coils are commonly influenced by attached structures. Thus, the structures of coiled-coil residues aberrantly attached to alternative proteins, such as those resulting from leukemogenic chromosomal rearrangements, may be distinguishable from those in normal tissues, and in turn serve as targets of selective drug design. The signs of helical staggers separated by between 13 and 30 residues are moderately yet significantly correlated, indicating that some of the coiled-coils transmit this conformational feature axially for at least 45 Å. A positive, albeit noisy, correlation also exists among tropomyosin coiled-coils for signed staggers separated by the 40-residue actin repeat distance, consistent with the semi-flexible tropomyosin filament binding F-actin and regulating skeletal muscle contraction in a partially cooperative manner. Communication of the signs of axial staggers is explained in part by minimization of main-chain hydrogen bond deformations. © Proteins 2013. © 2012 Wiley Periodicals, Inc.