title: (i, i + 4) Ion pairs stabilize helical peptides derived from smooth muscle caldesmon.
abstract: The central region of smooth muscle caldesmon contains 10 repeats of a 13-amino-acid residue motif that is rich in charged side chains. This region has been predicted to have a strong alpha-helical propensity, and the helical structure was thought to be stabilized by the interactions between oppositely charged side chains of residues at positions i and i + 4 (Wang, C.-L. A., Chalovich, J.M., Graceffa, P., Lu, R.C., Mabuchi, K, and Stafford, W.F., J.Biol. Chem. 266, 13958-13963, 1991). Two synthetic peptides corresponding to these repeats, each containing 25 and 60 amino acid residues, indeed assume an alpha-helical conformation that is stable over a wide range of salt concentration and pH, and exhibit a typical helix-coil transition upon heating. Most significantly, when the amino acid sequence of the 25-mer is randomized without losing the i-to-i + 4 ion pairs, the peptide maintains a helical content comparable to that of the wild-type peptide, whereas another peptide variant with a sequence rearranged to eliminate all i-to-(i + 4) ion pairs has much less helicity, suggesting that specific interactions between residues with (i,i + 4) spacings are important determinants for the maintenance of secondary structure in this region of caldesmon.
authors.affiliation: Muscle Research Group, Boston Biomedical Research Institute, Massachusetts 02114, USA. Wang@bbri.harvard.edu
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: C L
authors.initials: CL
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D002148:Calmodulin-Binding Proteins / Q000737:chemistry* / Q000187:drug effects; D002942:Circular Dichroism; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000187:drug effects; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012965:Sodium Chloride / Q000494:pharmacology; D014270:Trifluoroethanol / Q000494:pharmacology
chemical_list: D002148:Calmodulin-Binding Proteins; D006146:Guanidines; D007477:Ions; D010446:Peptide Fragments; D012965:Sodium Chloride; D014270:Trifluoroethanol; D019791:Guanidine