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Flexibility and Plasticity of Human Centrin 2 Binding to the Xeroderma Pigmentosum Group C Protein (XPC) from Nuclear Excision Repair,

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posted on 2006-03-21, 00:00 authored by Ao Yang, Simona Miron, Liliane Mouawad, Patricia Duchambon, Yves Blouquit, Constantin T. Craescu
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:  N847−R863). Here, we characterize the solution Ca2+-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 α 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 Ca2+-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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