1P059 Competitive binding of metal ions to the octarepeat region of human prion protein(01C. Protein : Property,Poster,The 52nd Annual Meeting of the Biophysical Society of Japan(BSJ2014))
1P059 オクタリピート領域をもつプリオンペプチドにおける金属との競合結合性(01C. 蛋白質 : 物性,ポスター,第52回日本生物物理学会年会(2014年度))

Masahiro Yagi, Kazuya Iwama, Haruto Onda, Wakako Hiraoka
2014 Seibutsu Butsuri  
Elucidation of the folding process of proteins is indispensable for understanding how proteins acquire a unique conformation. To this goal, we recently developed two-dimensional fluorescence lifetime correlation spectroscopy (2D FLCS). In the Biophysical society meeting last year, we reported a 2D FLCS study on the conformational transition dynamics of B domain of protein A (BdpA). The obtained results suggested that the conformational dynamics of BdpA occur within 10 microseconds. In this
more » ... , 2D FLCS was performed for two mutants of BdpA in which FRET pairs are attached on different positions. The results strongly suggested that the folding process of BdpA does not fit the simple two-state model. In the presentation, we discuss the folding mechanism of BdpA. 1P056 たった 10 残基から成るタンパク質の立体構造安定性に及ぼ す主鎖と側鎖の充填の効果 Effect of Backbone and Side-chain Packing on Structural Stability of the Protein with Only Ten Residues Satoshi Yasuda, Tomohiko Hayashi, Masahiro Kinoshita (IAE, kyoto Univ.) The small protein with only 10 residues, CLN025, folds into the β-hairpin structure. We show that the enthalpy increase arising from the break of hydrogen bonds with water molecules is compensated by the enthalpy decrease due to intramolecular hydrogen bonding. The water-entropy (WE) gain arising from close packing of the backbone and side chains including those with the four large aromatic residues is powerful enough to surpass the conformational-entropy (CE) loss. In its design template (GPM12) with only two aromatic residues, however, the WE gain yields to the CE loss though there is no enthalpy change, and the unfolded state is stabilized. The above elucidation is made possible by decomposing our free-energy function into physically insightful constituents. Human calcitonin (hCT) is a peptide hormone used as a medicine. It easily forms amyloid fibrils to reduce the efficiency. Salmon calcitonin (sCT) is known to inhibit amyloid formation of hCT. We revealed that the chimera peptides derived from sCT and hCT suppresses the amyloid formation. In order to develop an inhibitor of hCT amyloid formation, we aimed to clarify the inhibition mechanism. We measured the amyloid fibrillation process by thioflavin T fluorescence. The fluorescence intensity decreases with increasing the molar ratio of the chimera CT. The amyloid formation was completely suppressed by the equivalent amount of chimeric CT, indicating that hetero-dimer comprising hCT and the chimera CT forms at the initial process and inhibits the further fibrillation. 1P058 分子動力学シミュレーションを用いたリガンド結合による PR-Set7 の構造変化の研究 Molecular dynamics simulations for structure changes of PR- Set7 by ligand binding Takako Sakano, Hideaki Fujitani (RCAST, UTokyo) X-ray crystal structure of a target protein is used to find new active molecules, Virtual Screening, or their docking pose prediction. However, some X-ray crystal structures are not suitable for such purposes, because some proteins significantly change their structure by allosteric effect of ligand binding. We obtained apo structure of histone methyltransferase PR-Set7 by molecular dynamic simulations started from the X-ray crystal structure (PDB:1ZKK) without histone H4 peptide and other cofactor. We predicted docking poses of known ligands to the apo-PR-Set7 with some tools, and performed MD simulations of them. We present the results: how the structures differ and how they effect ligand docking. 1P059 オクタリピート領域をもつプリオンペプチドにおける金属と の競合結合性 Competitive binding of metal ions to the octarepeat region of human prion protein Masahiro Yagi, Kazuya Iwama, Haruto Onda, Wakako Hiraoka (Dept. Phys., Grad. Sch. Sci. & Tech., Meiji Univ.) The misfolded form of prion protein (PrP) cause neurodegenerative diseases. It is thought that the binding of PrP to Cu 2+ may result in the misfolding of PrP. To clarify the process of misfolding and subsequent aggregation, we investigated the structure of the octarepeat peptide (PHGGGWGQ) of human PrP that binds to Cu 2+ and the stability of this bound structure. ESR spectra indicated two kinds of coordination modes for the binding of peptide -Cu 2+ . Competitive binding of other divalent metal ions, such as Co 2+ , Ni 2+ , Zn 2+ , and Mn 2+ , to peptide-Cu 2+ revealed that these metal ions were partially substitute for Cu 2+ . These results suggest that the stability of PrP-Cu 2+ is possibly affected by the presence of other metal ions. 1P060 粗視化 MD-SAXS 法の開発 Development of Coarse-Grained MD-SAXS method
doi:10.2142/biophys.54.s150_5 fatcat:z7ldwzj24bcddafu4bq3xnfvde