%0 Journal Article
%T Identification of two Amino Acids in the C-terminal Domain of Mouse CRY2 Essential for PER2 Interaction
%A Natali Ozber
%A Ibrahim Baris
%A Gulnaz Tatlici
%A Ibrahim Gur
%A Seda Kilinc
%A Evrim B Unal
%A Ibrahim H Kavakli
%J BMC Molecular Biology
%D 2010
%I BioMed Central
%R 10.1186/1471-2199-11-69
%X We identified a region on mCRY2 (between residues 493 and 512) responsible for direct physical interaction with mPER2 by mammalian two-hybrid and co-immunoprecipitation assays. Moreover, using oligonucleotide-based degenerate PCR, we discovered that mutation of Arg-501 and Lys-503 of mCRY2 within this C-terminal region totally abolishes interaction with PER2.Our results identify mCRY2 amino acid residues that interact with the mPER2 binding region and suggest the potential for rational drug design to inhibit CRYs for specific therapeutic approaches.Circadian rhythms are oscillations in the behaviour and biochemical reactions of organisms and occur with a periodicity of approximately 24 hours [1]. Traditionally, the circadian system has been conceptualized in terms of three components: an input component, a clockwork component and an output component. Recent studies, however, have shown that there are considerable overlaps between the three components at both macroscopic and microscopic levels, such that the three components may be organized into multiple interconnecting pathways [2,3]. In mammals, the input component is mediated at the macroscopic level by the visual perception of light. The master circadian clock is located in the hypothalamus as a pair of neuron clusters that are known as the suprachiasmatic nuclei (SCN). The output component is elaborated by endocrine mechanisms in the form of prokineticin (PK2) and, transforming growth factor-¦Á (TGF-¦Á) secretion [4,5] from the SCN which also engage other regions of the brain through neural connections. At the molecular level, the clockwork of the SCN involves several proteins that participate in positive and negative transcriptional feedback loops. The mammalian BMAL1 and CLOCK are the transcription factors that contain two basic helix-loop-helix domains and bind E-box elements (CACGTG) in the Period and Cryptochrome clock genes and activate their transcription (the positive arm of the feedback loop) [4-6]. The
%U http://www.biomedcentral.com/1471-2199/11/69