Flexibility and plasticity of human centrin 2 binding to the xeroderma pigmentosum group C protein (XPC) from nuclear excision repair

Biochemistry
Ao YangConstantin T Craescu

Abstract

Human centrin 2 is a component of the nucleotide excision repair system, as a subunit of the heterotrimer including xeroderma pigmentosum group C protein (XPC) and hHR23B. The C-terminal domain of centrin (C-HsCen2) binds strongly a peptide from the XPC protein (P1-XPC: N(847)-R(863)). Here, we characterize the solution Ca(2+)-dependent structural and molecular features of the C-HsCen2 in complex with P1-XPC, mainly using NMR spectroscopy and molecular modeling. The N-terminal half of the peptide, organized as an alpha helix is anchored into a deep hydrophobic cavity of the protein, because of three bulky hydrophobic residues in position 1-4-8 and electrostatic contacts with the centrin helix E. Investigation of the whole centrin interactions shows that the N-terminal domain of the protein is not involved in the complex formation and is structurally independent from the peptide-bound C-terminal domain. The complex may exist in three different binding conformations corresponding to zero, one, and two Ca(2+)-bound states, which may exchange with various rates and have distinct structural stability. The various features of the intermolecular interaction presented here constitute a centrin-specific mode for the target binding.

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Citations

Nov 26, 2008·Journal of Biomolecular NMR·Liliya Vugmeyster, C James McKnight
Jul 6, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Jean Baptiste CharbonnierConstantin T Craescu
Dec 28, 2007·Molecular and Cellular Biology·Li Chen, Kiran Madura
Jul 20, 2012·Biochemistry. Biokhimii︠a︡·Y S KrasikovaO I Lavrik
Jan 19, 2016·Biochimica Et Biophysica Acta·Juan Martinez-Sanz, Liliane Assairi
Nov 2, 2015·Cellular and Molecular Life Sciences : CMLS·Marjo-Riitta PuumalainenHanspeter Naegeli
Sep 2, 2008·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Zhao YaqinYang Binsheng
Mar 18, 2008·DNA Repair·Deborah L CroteauBennett Van Houten
Mar 11, 2008·Progress in Retinal and Eye Research·Philipp TrojanUwe Wolfrum
Dec 7, 2007·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Yaqin ZhaoBinsheng Yang
Sep 28, 2007·Journal of Molecular Biology·Jean-Baptiste CharbonnierConstantin T Craescu
Jul 3, 2007·Free Radical Biology & Medicine·Yves BlouquitCécile Sicard-Roselli
Jul 31, 2014·Environmental and Molecular Mutagenesis·Dariya MomotOfelia A Olivero
Oct 28, 2009·Journal of Molecular Biology·Juan Martinez-SanzConstantin T Craescu
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Nov 9, 2017·Metallomics : Integrated Biometal Science·Enxian ShiBinsheng Yang
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Dec 7, 2007·Journal of Cell Science·Delphine GogendeauJanine Beisson
Jun 9, 2021·Nature Communications·Trevor van EeuwenKenji Murakami

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