Download MendeleyC-terminal half of human centrin 2 behaves like a regulatory EF-hand domain
Matei, E., Miron, S., Blouquit, Y., Duchambon, P., Durussel, P., Cox, J.A., Craescu, C.T.(2003) Biochemistry 42: 1439-1450
- PubMed: 12578356
- DOI: https://doi.org/10.1021/bi0269714
- Primary Citation of Related Structures:
1M39 - PubMed Abstract:
Human centrin 2 (HsCen2) is an EF-hand protein that plays a critical role in the centrosome duplication and separation during cell division. We studied the structural and Ca(2+)-binding properties of two C-terminal fragments of this protein: SC-HsCen2 (T94-Y172), covering two EF-hands, and LC-HsCen2 (M84-Y172), having 10 additional residues. Both fragments are highly disordered in the apo state but become better structured (although not conformationally homogeneous) in the presence of Ca(2+) and depending on the nature of the cations (K(+) or Na(+)) in the buffer. Only the longer C-terminal domain, in the Ca(2+)-saturated state and in the presence of Na(+) ions, was amenable to structure determination by nuclear magnetic resonance. The solution structure of LC-HsCen2 reveals an open two EF-hand structure, similar to the conformation of related Ca(2+)-saturated regulatory domains. Unexpectedly, the N-terminal helix segment (F86-T94) lies over the exposed hydrophobic cavity. This unusual intramolecular interaction increases considerably the Ca(2+) affinity and constitutes a useful model for the target binding.
Organizational Affiliation:
INSERM U350 and Institut Curie-Recherche, Centre Universitaire, Bâtiments 110-112, 91405 Orsay, France.
