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    Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly


    Fadda, Elisa (2016) Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly. Computational and Structural Biotechnology Journal, 14. pp. 78-85. ISSN 2001-0370

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    Abstract

    Lack of structure is often an essential functional feature of protein domains. The coordination of macromolecular assemblies in DNA repair pathways is yet another task disordered protein regions are highly implicated in. Here I review the available experimental and computational data and within this context discuss the functional role of structure and disorder in one of the essential scaffolding proteins in the nucleotide excision repair (NER) pathway, namely Xeroderma pigmentosum complementation group A (XPA). From the analysis of the current knowledge, in addition to protein–protein docking and secondary structure prediction results presented for the first time herein, a mechanistic framework emerges, where XPA builds the NER pre-incision complex in a modular fashion, as “beads on a string”, where the protein–protein interaction “beads”, or modules, are interconnected by disordered link regions. This architecture is ideal to avoid the expected steric hindrance constraints of the DNA expanded bubble. Finally, the role of the XPA structural disorder in binding affinity modulation and in the sequential binding of NER core factors in the pre-incision complex is also discussed.

    Item Type: Article
    Keywords: Structurally disordered protein domains; Nucleotide Excision Repair (XPA); NER pre-incision complex; Beads-on-a-string multiprotein complex; XPA; RPA; ERCC1-XPF; Conformational selection; Molecular recognition;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 12537
    Identification Number: https://doi.org/10.1016/j.csbj.2015.11.007
    Depositing User: Elisa Fadda
    Date Deposited: 06 Mar 2020 17:10
    Journal or Publication Title: Computational and Structural Biotechnology Journal
    Publisher: Elsevier
    Refereed: Yes
    URI:

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