Ca 2+-induced self-assembly in designed peptides with optimally spaced gamma-carboxyglutamic acid residues |
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Authors: | Dai Qiuyun Dong Mingxin Liu Zhuguo Prorok Mary Castellino Francis J |
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Institution: | a Institute of Biotechnology, Beijing 100071, Chinab Department of Chemistry and Biochemistry, University of Notre Dame, IN 46556, USAc W.M. Keck Center for Transgene Research, University of Notre Dame, IN 46556, USA |
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Abstract: | We have previously elucidated a new paradigm for the metal ion-induced helix-helix assembly in the natural γ-carboxyglutamic acid (Gla)-containing class of conantokin (con) peptides, typified by con-G and a variant of con-T, con-TK7Gla], independent of the hydrophobic effect. In these “metallo-zipper” structures, Gla residues spaced at i, i + 4, i + 7, i + 11 intervals, which is similar to the arrangement of a and d residues in typical heptads of coiled-coils, coordinate with Ca2+ and form specific antiparallel helical dimers. In order to evaluate the common role of Gla residues in peptide self-assembly, we extend herein the same Gla arrangement to designed peptides: NH2-(γLSγEAK)3-CONH2 (peptide 1) and NH2-γLSγEAKγLSγQANγLSγKAE-CONH2 (peptide 2). Peptide 1 and peptide 2 exhibit no helicity alone, but undergo structural transitions to helical conformations in the presence of a variety of divalent cations. Sedimentation equilibrium ultracentrifugation analyses showed that peptide 1 and peptide 2 form helical dimers in the presence of Ca2+, but not Mg2+. Folding and thiol-disulfide rearrangement assays with Cys-containing peptide variants indicated that the helical dimers are mixtures of antiparallel and parallel dimers, which is different from the strict antiparallel strand orientations of con-G and con-TK7γGla] dimers. These findings suggest that the Gla arrangement, i, i + 4, i + 7, i + 11, i + 14, plays a key role in helix formation, without a strict adherence to strand orientation of the helical dimer. |
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Keywords: | gamma-carboxyglutamic acid Helix-helix interactions Peptide self-assembly |
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