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    The role of conformational selection in the molecular recognition of the wild type and mutants XPA67‐80 peptides by ERCC1

    Fadda, Elisa (2015) The role of conformational selection in the molecular recognition of the wild type and mutants XPA67‐80 peptides by ERCC1. Proteins, 83. pp. 1341-1351. ISSN 1097-0134

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    Molecular recognition is a fundamental step in the coordination of biomolecular pathways. Understanding how recognition and binding occur between highly flexible protein domains is a complex task. The conformational selection theory provides an elegant rationalization of the recognition mechanism, especially valid in cases when unstructured protein regions are involved. The recognition of a poorly structured peptide, namely XPA67‐80, by its target receptor ERCC1, falls in this challenging study category. The microsecond molecular dynamics (MD) simulations, discussed in this work, show that the conformational propensity of the wild type XPA67‐80 peptide in solution supports conformational selection as the key mechanism driving its molecular recognition by ERCC1. Moreover, all the mutations of the XPA67‐80 peptide studied here cause a significant increase of its conformational disorder, relative to the wild type. Comparison to experimental data suggests that the loss of the recognized structural motifs at the microscopic time scale can contribute to the critical decrease in binding observed for one of the mutants, further substantiating the key role of conformational selection in recognition. Ultimately, because of the high sequence identity and analogy in binding, it is conceivable that the conclusions of this study on the XPA67‐80 peptide also apply to the ERCC1‐binding domain of the XPA protein.

    Item Type: Article
    Keywords: molecular recognition; conformational selection; induced fit; XPA-ERCC1; nucleotide excision repair; molecular dynamics; disordered proteins; conformational flexibility;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 10196
    Identification Number:
    Depositing User: Elisa Fadda
    Date Deposited: 08 Nov 2018 17:39
    Journal or Publication Title: Proteins
    Publisher: Wiley
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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