Flexibility and Plasticity of Human Centrin 2 Binding to the Xeroderma Pigmentosum Group C Protein (XPC) from Nuclear Excision Repair
详细信息 查看全文
- 作者：Ao Yang ; Simona Miron ; Liliane Mouawad ; Patricia Duchambon ; Yves Blouquit ; and Constantin T. Craescu
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：March 21, 2006
- 年：2006
- 卷：45
- 期：11
- 页码：3653 - 3663
- 全文大小：538K
- 年卷期：v.45,no.11(March 21, 2006)
- ISSN：1520-4995
文摘
Human centrin 2 is a component of the nucleotide excision repair system, as a subunit of theheterotrimer including xeroderma pigmentosum group C protein (XPC) and hHR23B. The C-terminaldomain 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 incomplex with P1-XPC, mainly using NMR spectroscopy and molecular modeling. The N-terminal halfof the peptide, organized as an 
helix is anchored into a deep hydrophobic cavity of the protein, becauseof three bulky hydrophobic residues in position 1-4-8 and electrostatic contacts with the centrin helixE. Investigation of the whole centrin interactions shows that the N-terminal domain of the protein is notinvolved in the complex formation and is structurally independent from the peptide-bound C-terminaldomain. The complex may exist in three different binding conformations corresponding to zero, one, andtwo Ca2+-bound states, which may exchange with various rates and have distinct structural stability. Thevarious features of the intermolecular interaction presented here constitute a centrin-specific mode for thetarget binding.
helix is anchored into a deep hydrophobic cavity of the protein, becauseof three bulky hydrophobic residues in position 1-4-8 and electrostatic contacts with the centrin helixE. Investigation of the whole centrin interactions shows that the N-terminal domain of the protein is notinvolved in the complex formation and is structurally independent from the peptide-bound C-terminaldomain. The complex may exist in three different binding conformations corresponding to zero, one, andtwo Ca2+-bound states, which may exchange with various rates and have distinct structural stability. Thevarious features of the intermolecular interaction presented here constitute a centrin-specific mode for thetarget binding.