Peer-Reviewed Journal Details
Mandatory Fields
Fadda E.
2016
January
Computational and Structural Biotechnology Journal
Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly
Published
21 ()
Optional Fields
Beads-on-a-string multiprotein complex Conformational selection ERCC1-XPF Molecular recognition NER pre-incision complex Nucleotide Excision Repair (XPA) RPA Structurally disordered protein domains XPA
14
78
85
© 2015 The Author. 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.
2001-0370
10.1016/j.csbj.2015.11.007
Grant Details