Conformational determinants for the recruitment of ERCC1 by XPA in the nucleotide excision repair (NER) pathway: structure and dynamics of the XPA binding motif
Conformational determinants for the recruitment of ERCC1 by XPA in the nucleotide excision repair (NER) pathway: structure and dynamics of the XPA binding motif
XPA is an essential protein in the nucleotide excision repair (NER) pathway, in charge of recruiting the ERCC1-XPF endonuclease complex to the DNA damage site. The only currently available structural insight into the binding of XPA to ERCC1 derives from the solution NMR structure of a complex between the ERCC1 central fragment and a 14-residue peptide, corresponding to the highly conserved binding motif of the XPA N-terminus, XPA67-80. The extensive all-atom molecular-dynamics simulation study of the XPA 67-80 peptide both bound to the ERCC1 central fragment and free in solution presented here completes the profile of the structural determinants responsible for the ERCC1/XPA67-80 complex stability. In addition to the wild-type, this study also looks at specific XPA67-80 mutants in complex with the ERCC1 central domain and thus contributes to defining the conformational determinants for binding, as well as all of the essential structural elements necessary for the rational design of an XPA-based, ERCC1-specific inhibitor.
2503-2511
Fadda, Elisa
11ba1755-9585-44aa-a38e-a8bcfd766abb
4 June 2013
Fadda, Elisa
11ba1755-9585-44aa-a38e-a8bcfd766abb
Fadda, Elisa
(2013)
Conformational determinants for the recruitment of ERCC1 by XPA in the nucleotide excision repair (NER) pathway: structure and dynamics of the XPA binding motif.
Biophysical Journal, 104 (11), .
(doi:10.1016/j.bpj.2013.04.023).
Abstract
XPA is an essential protein in the nucleotide excision repair (NER) pathway, in charge of recruiting the ERCC1-XPF endonuclease complex to the DNA damage site. The only currently available structural insight into the binding of XPA to ERCC1 derives from the solution NMR structure of a complex between the ERCC1 central fragment and a 14-residue peptide, corresponding to the highly conserved binding motif of the XPA N-terminus, XPA67-80. The extensive all-atom molecular-dynamics simulation study of the XPA 67-80 peptide both bound to the ERCC1 central fragment and free in solution presented here completes the profile of the structural determinants responsible for the ERCC1/XPA67-80 complex stability. In addition to the wild-type, this study also looks at specific XPA67-80 mutants in complex with the ERCC1 central domain and thus contributes to defining the conformational determinants for binding, as well as all of the essential structural elements necessary for the rational design of an XPA-based, ERCC1-specific inhibitor.
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Published date: 4 June 2013
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Local EPrints ID: 499773
URI: http://eprints.soton.ac.uk/id/eprint/499773
ISSN: 0006-3495
PURE UUID: 2f67ed5e-7a48-42c3-9efe-97b4ba0815bd
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Date deposited: 03 Apr 2025 16:47
Last modified: 04 Apr 2025 02:10
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Author:
Elisa Fadda
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