Abstract
Cln1 and Cln2, G1/S cyclins of the ascomycetous budding yeast Saccharomyces cerevisiae (S. cerevisiae), oscillate during the cell cycle, rising in late G1 and falling in early S phase. We have been tried to elucidate the structure basis of the functional distinction between Cln1 and Cln2. Here we performed in silico simulations: construction and evaluation of three dimensional structures of Cln1-Cdc28 and Cln2-Cdc28 complexes. Our in silico simulations suggested that the interaction of Cln1 and Cln2 with Cdc28 were in the two distinct situations, designated as flip and flop conformation, at the extra amino acid region in the cyclin box of Cln1 and Cln2. We speculated the trigger of this flip-flop conversion of the extra amino acid region in the cyclin box of Cln1-Cdc28 and Cln2-Cdc28 might be regulated by the ubiquitination of the sequences rich in Pro (P), Glu (E), Ser (S) and Thr (T), so-called PEST motifs, in Cln1 and Cln2. Furthermore, we presumed that the functional superiority between Cln1 and Cln2 in the G1/S phase of S. cerevisiae might be controlled by flip-flop conversion and ubiquitin-proteasome pathway.
Highlights
The control system of cell cycle is the regulatory network that governs the order and timing of cell cycle events
To clarify the structure-function relationship of G1/S cyclins of S. cerevisiae, we performed in silico simulations [26]: construction of three dimensional (3D) structure by homology modeling [27,28], optimization of 3D structure by molecular mechanics calculations and molecular dyanamics (MD) simulations [29], evaluation of interaction energy (IE) [30] and electrostatic complementarity (EC) [22] of Cln1-Cdc28 and Cln2-Cdc28 complexes
To sufficiently analyze the structural properties of G1/S cyclins of S. cerevisiae, we constructed the 3D structure of Cln1-Cdc28 and Cln2Cdc28
Summary
The control system of cell cycle is the regulatory network that governs the order and timing of cell cycle events. Cyclins are highly conserved proteins that activate CDKs to regulate the cell cycle, transcription and other cellular processes. These different cyclin types are produced at different cell cycle stage to accumulate at specific times during the cell cycle, leading to waves of activation of distinct cyclin/ Cdk complexes. The timing of START, a major control point at the G1/S transition, in S. cerevisiae cells are controlled principally by G1 cyclin Cln and G1/S cyclins Cln and Cln2 [6] Each of these three cyclins contains a sequence motif conserved among all of them, which is thought to mediate their association with the cell cycle regulatory kinase Cdc28 [7]. Cln, its protein and kinase activity levels are no oscillation throughout the cell cycle, activates a transcription program mediated by the transcriptional factors SBF and MBF that regulate the rate of G1 progression in S. cerevisiae (Figure 1) [9,10,11,12]
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