文献类型：期刊文献

英文题名：Visualizing chaperone-assisted protein folding

作者：Horowitz, Scott[1,2];Salmon, Loic[1,2];Koldewey, Philipp[1,2];Ahlstrom, Logan S.[1,2,3];Martin, Raoul[1,2,9];Quan, Shu[4];Afonine, Pavel V.[5];van den Bedem, Henry[6];Wang, Lili[1,2];Xu, Qingping[7];Trievel, Raymond C.[8];Brooks, Charles L., III[3];Bardwell, James C. A.[1,2]

机构：[1]Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA;[2]Howard Hughes Med Inst, Ann Arbor, MI USA;[3]Univ Michigan, Dept Chem & Biophys Program, Ann Arbor, MI USA;[4]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomfg, Shanghai, Peoples R China;[5]Lawrence Berkeley Natl Lab, Berkeley, CA USA;[6]Stanford Univ, SLAC Natl Accelerator Lab, Div Biosci, Stanford, CA USA;[7]SLAC Natl Lab, Stanford Synchrotron Radiat Lightsource, Joint Ctr Struct Genom, Menlo Pk, CA USA;[8]Univ Michigan, Dept Biol Chem, Ann Arbor, MI USA;[9]Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA USA

年份：2016

卷号：23

期号：7

起止页码：691

外文期刊名：NATURE STRUCTURAL & MOLECULAR BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000379368200011)】；

基金：The authors would like to thank J. Smith, D. Akey, U. Jakob, D. Smith, Z. Wawrzak, and F. Stull for critical comments and suggestions. Use of the Advanced Photon Source, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the US DOE under contract no. DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (grant 085P1000817). This work was funded by an NRSA National Institutes of Health (NIH) grant GM108298 (L.S.A.), a Boehringer Ingelheim Fonds fellowship (P.K.), a National Natural Science Foundation of China (NSFC) grant 31400664 (S.Q.), the Shanghai Pujiang Program (S.Q.), NIH grant GM102829 (J.C.A.B.), NIH grant GM107233 (C.L.B.), NIH grant 1P01 GM063210 (P.V.), the Phenix Industrial Consortium and the US Department of Energy Contract No. DE-AC02-05CH11231 (RV.) and NSF grant CHE1506273 (C.L.B.). J.C.A.B. is supported as a Howard Hughes Medical Institute Investigator.

语种：英文

摘要：Challenges in determining the structures of heterogeneous and dynamic protein complexes have greatly hampered past efforts to obtain a mechanistic understanding of many important biological processes. One such process is chaperone assisted protein folding. Obtaining structural ensembles of chaperone-substrate complexes would ultimately reveal how chaperones help proteins fold into their native state. To address this problem, we devised a new structural biology approach based on X-ray crystallography, termed residual electron and anomalous density (READ). READ enabled us to visualize even sparsely populated conformations of the substrate protein immunity protein 7 (Im7) in complex with the Escherichia coli chaperone Spy, and to capture a series of snapshots depicting the various folding states of Im7 bound to Spy. The ensemble shows that Spy-associated Im7 samples conformations ranging from unfolded to partially folded to native-like states and reveals how a substrate can explore its folding landscape while being bound to a chaperone.