4YUJ

Multiconformer synchrotron model of CypA at 240 K

4YUJ の概要

• エントリーDOI: 10.2210/pdb4yuj/pdb
• 関連するPDBエントリー: 4YUG 4YUH 4YUI 4YUK 4YUL 4YUM 4YUN 4YUO 4YUP
• 分子名称: Peptidyl-prolyl cis-trans isomerase A (2 entities in total)
• 機能のキーワード: cyclophilin, isomerase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P62937
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18036.50

構造登録者

Keedy, D.A.,Kenner, L.R.,Warkentin, M.,Woldeyes, R.A.,Thompson, M.C.,Brewster, A.S.,Van Benschoten, A.H.,Baxter, E.L.,Hopkins, J.B.,Uervirojnangkoorn, M.,McPhillips, S.E.,Song, J.,Mori, R.A.,Holton, J.M.,Weis, W.I.,Brunger, A.T.,Soltis, M.,Lemke, H.,Gonzalez, A.,Sauter, N.K.,Cohen, A.E.,van den Bedem, H.,Thorne, R.E.,Fraser, J.S. (登録日: 2015-03-18, 公開日: 2015-10-14, 最終更新日: 2023-09-27)

主引用文献

Keedy, D.A.,Kenner, L.R.,Warkentin, M.,Woldeyes, R.A.,Hopkins, J.B.,Thompson, M.C.,Brewster, A.S.,Van Benschoten, A.H.,Baxter, E.L.,Uervirojnangkoorn, M.,McPhillips, S.E.,Song, J.,Alonso-Mori, R.,Holton, J.M.,Weis, W.I.,Brunger, A.T.,Soltis, S.M.,Lemke, H.,Gonzalez, A.,Sauter, N.K.,Cohen, A.E.,van den Bedem, H.,Thorne, R.E.,Fraser, J.S.
Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography.
Elife, 4:-, 2015

PubMed Abstract: Determining the interconverting conformations of dynamic proteins in atomic detail is a major challenge for structural biology. Conformational heterogeneity in the active site of the dynamic enzyme cyclophilin A (CypA) has been previously linked to its catalytic function, but the extent to which the different conformations of these residues are correlated is unclear. Here we compare the conformational ensembles of CypA by multitemperature synchrotron crystallography and fixed-target X-ray free-electron laser (XFEL) crystallography. The diffraction-before-destruction nature of XFEL experiments provides a radiation-damage-free view of the functionally important alternative conformations of CypA, confirming earlier synchrotron-based results. We monitored the temperature dependences of these alternative conformations with eight synchrotron datasets spanning 100-310 K. Multiconformer models show that many alternative conformations in CypA are populated only at 240 K and above, yet others remain populated or become populated at 180 K and below. These results point to a complex evolution of conformational heterogeneity between 180--240 K that involves both thermal deactivation and solvent-driven arrest of protein motions in the crystal. The lack of a single shared conformational response to temperature within the dynamic active-site network provides evidence for a conformation shuffling model, in which exchange between rotamer states of a large aromatic ring in the middle of the network shifts the conformational ensemble for the other residues in the network. Together, our multitemperature analyses and XFEL data motivate a new generation of temperature- and time-resolved experiments to structurally characterize the dynamic underpinnings of protein function.

PubMed: 26422513
DOI: 10.7554/eLife.07574

実験手法

X-RAY DIFFRACTION (1.42 Å)