Structure-function analysis of the EF-hand protein centrin-2 for its intracellular localization and nucleotide excision repair
2013
Centrin-2 is an evolutionarily conserved, calmodulin-related protein, which is involved in multiple cellular functions including
centrosomeregulation and
nucleotide excision repair(NER) of DNA. Particularly to exert the latter function, complex formation with the XPC protein, the pivotal NER damage recognition factor, is crucial. Here, we show that the C-terminal half of
centrin-2, containing two calcium-binding
EF-handmotifs, is necessary and sufficient for both its localization to the
centrosomeand interaction with XPC. In XPC-deficient cells, nuclear localization of overexpressed
centrin-2 largely depends on co-overexpression of XPC, and mutational analyses of the C-terminal domain suggest that XPC and the major binding partner in the
centrosomeshare a common binding surface on the
centrin-2 molecule. On the other hand, the N-terminal domain of
centrin-2 also contains two
EF-handmotifs but shows only low-binding affinity for calcium ions. Although the N-terminal domain is dispensable for enhancement of the DNA damage recognition activity of XPC, it contributes to augmenting rather weak physical interaction between XPC and XPA, another key factor involved in NER. These results suggest that
centrin-2 may have evolved to bridge two protein factors, one with high affinity and the other with low affinity, thereby allowing delicate regulation of various biological processes.
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