β-Bulges: Extensive structural analyses of β-sheets irregularities

Authors

  • Pierrick Craveur,

    Corresponding author
    1. University of Paris Diderot, Sorbonne Paris Cité, Paris, France
    2. Institut National de la Transfusion Sanguine (INTS), Paris, France
    3. Laboratoire d'Excellence GR-Ex, Paris, France
    • INSERM, Paris, France
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  • Agnel Praveen Joseph,

    1. National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
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  • Joseph Rebehmed,

    1. INSERM, Paris, France
    2. University of Paris Diderot, Sorbonne Paris Cité, Paris, France
    3. Institut National de la Transfusion Sanguine (INTS), Paris, France
    4. Laboratoire d'Excellence GR-Ex, Paris, France
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  • Alexandre G. de Brevern

    Corresponding author
    1. University of Paris Diderot, Sorbonne Paris Cité, Paris, France
    2. Institut National de la Transfusion Sanguine (INTS), Paris, France
    3. Laboratoire d'Excellence GR-Ex, Paris, France
    • INSERM, Paris, France
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Correspondence to: de Brevern Alexandre G., INSERM UMR-S 665, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Université Denis Diderot, Sorbonne Paris Cité 7, INTS, 6, rue Alexandre Cabanel, 75739 Paris cedex 15, France. E-mail: alexandre.debrevern@univ-paris-diderot.fr (or) Craveur Pierrick, INSERM UMR-S 665, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Université Denis Diderot, Sorbonne Paris Cité 7, INTS, 6, rue Alexandre Cabanel, 75739 Paris cedex 15, France. E-mail: pierrick.craveur@inserm.fr

Abstract

β-Sheets are quite frequent in protein structures and are stabilized by regular main-chain hydrogen bond patterns. Irregularities in β-sheets, named β-bulges, are distorted regions between two consecutive hydrogen bonds. They disrupt the classical alternation of side chain direction and can alter the directionality of β-strands. They are implicated in protein-protein interactions and are introduced to avoid β-strand aggregation. Five different types of β-bulges are defined. Previous studies on β-bulges were performed on a limited number of protein structures or one specific family. These studies evoked a potential conservation during evolution. In this work, we analyze the β-bulge distribution and conservation in terms of local backbone conformations and amino acid composition. Our dataset consists of 66 times more β-bulges than the last systematic study (Chan et al. Protein Science 1993, 2:1574–1590). Novel amino acid preferences are underlined and local structure conformations are highlighted by the use of a structural alphabet. We observed that β-bulges are preferably localized at the N- and C-termini of β-strands, but contrary to the earlier studies, no significant conservation of β-bulges was observed among structural homologues. Displacement of β-bulges along the sequence was also investigated by Molecular Dynamics simulations.

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