Conformational heterogeneity in tails of DNA-binding proteins is augmented by proline containing repeats. Issue 12 (6th November 2017)

• Record Type: Journal Article
• Authors: Khare, Harshavardhan; Dey, Debayan; Madhu, Chilakapati; Senapati, Dillip; Raghothama, Srinivasarao; Govindaraju, Thimmaiah; Ramakumar, Suryanarayanarao
• Is Part Of: Molecular bioSystems. Volume 13:Issue 12(2017)
• Page Start: 2531
• Page End: 2544
• Publication Date: 2017-11-06
• Subjects: Molecular biology -- Periodicals; Biochemistry -- Periodicals; 571.7405
• DOI: 10.1039/c7mb00412e
• Languages: English
• ISSNs: 1742-206X

Abstract

Abstract : We model intrinsically disordered peptides mimicking the tails of DNA-binding proteins and propose parameters for the design of intrinsic disorder. Abstract : A cationic terminal extension or tail is a common feature of many DNA-binding proteins. We show that a particular type of tail rich in proline, alanine and lysine belongs to the class of 'flexible disorder' and consists of characteristic pentapeptide repeats. Our designed peptides, (AAKKA)1–4 and (PAKKA)1–4, represent the tails of several bacterial DNA-binding proteins. Enhanced conformational sampling of these representative peptides using accelerated molecular dynamic simulations supported by circular dichroism spectroscopy and nuclear magnetic resonance studies demonstrates the role of frequent and interspersed prolines in augmenting conformational heterogeneity of the peptide backbone. Analysis of circular variance of backbone dihedral angles indicates alternating regions of relative rigidity and flexibility along the peptide sequence due to prolines. Preferred placement of lysines in the regions of higher backbone flexibility might improve DNA-binding by conformational selection. Our results could be relevant for rational de novo design of disordered peptides.