globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1807379115
论文题名:
The consequences of cavity creation on the folding landscape of a repeat protein depend upon context
作者: Jenkins K.A.; Fossat M.J.; Zhang S.; Rai D.K.; Klein S.; Gillilan R.; White Z.; Gerlich G.; McCallum S.A.; Winter R.; Gruner S.M.; Barrick D.; Royer C.A.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2018
卷: 115, 期:35
起始页码: E8153
结束页码: E8161
语种: 英语
英文关键词: Cooperativity ; High pressure ; NMR ; Repeat protein folding ; SAXS
Scopus关键词: leucine rich repeat protein pp32 ; protein ; unclassified drug ; urea ; ANP32A protein, human ; signal peptide ; amino terminal sequence ; Article ; carboxy terminal sequence ; controlled study ; hyperbarism ; nuclear magnetic resonance spectroscopy ; priority journal ; protein cavity creation ; protein folding ; protein motif ; protein stability ; protein structure ; protein unfolding ; thermodynamics ; X ray crystallography ; chemistry ; genetics ; human ; mutation ; nuclear magnetic resonance ; protein domain ; protein folding ; small angle scattering ; structure activity relation ; X ray diffraction ; Humans ; Intracellular Signaling Peptides and Proteins ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Protein Domains ; Protein Folding ; Protein Stability ; Scattering, Small Angle ; Structure-Activity Relationship ; X-Ray Diffraction
英文摘要: The effect of introducing internal cavities on protein native structure and global stability has been well documented, but the consequences of these packing defects on folding free-energy landscapes have received less attention. We investigated the effects of cavity creation on the folding landscape of the leucine-rich repeat protein pp32 by high-pressure (HP) and urea-dependent NMR and high-pressure small-angle X-ray scattering (HPSAXS). Despite a modest global energetic perturbation, cavity creation in the N-terminal capping motif (N-cap) resulted in very strong deviation from two-state unfolding behavior. In contrast, introduction of a cavity in the most stable, C-terminal half of pp32 led to highly concerted unfolding, presumably because the decrease in stability by the mutations attenuated the N- to C-terminal stability gradient present in WT pp32. Interestingly, enlarging the central cavity of the protein led to the population under pressure of a distinct intermediate in which the N-cap and repeats 1–4 were nearly completely unfolded, while the fifth repeat and the C-terminal capping motif remained fully folded. Thus, despite modest effects on global stability, introducing internal cavities can have starkly distinct repercussions on the conformational landscape of a protein, depending on their structural and energetic context. © National Academy of Sciences. All rights reserved.
Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163670
Appears in Collections:气候变化与战略

Files in This Item:

There are no files associated with this item.


作者单位: Jenkins, K.A., Graduate Program in Biochemistry and Biophysics, Rensselaer Polytechnic Institute, Troy, NY 12180, United States; Fossat, M.J., Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, United States, Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, United States; Zhang, S., Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, United States; Rai, D.K., Cornell High Energy Synchrotron Source, Cornell University, Ithaca, NY 14853, United States; Klein, S., T. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States; Gillilan, R., Cornell High Energy Synchrotron Source, Cornell University, Ithaca, NY 14853, United States; White, Z., Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, United States; Gerlich, G., Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, United States; McCallum, S.A., Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, United States; Winter, R., Department of Physical Chemistry, Technical University of Dortmund, Dortmund, 44227, Germany; Gruner, S.M., Cornell High Energy Synchrotron Source, Cornell University, Ithaca, NY 14853, United States, Department of Physics, Cornell University, Ithaca, NY 14853, United States, Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY 14853, United States; Barrick, D., T. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, United States; Royer, C.A., Graduate Program in Biochemistry and Biophysics, Rensselaer Polytechnic Institute, Troy, NY 12180, United States, Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, United States, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, United States

Recommended Citation:
Jenkins K.A.,Fossat M.J.,Zhang S.,et al. The consequences of cavity creation on the folding landscape of a repeat protein depend upon context[J]. Proceedings of the National Academy of Sciences of the United States of America,2018-01-01,115(35)
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Jenkins K.A.]'s Articles
[Fossat M.J.]'s Articles
[Zhang S.]'s Articles
百度学术
Similar articles in Baidu Scholar
[Jenkins K.A.]'s Articles
[Fossat M.J.]'s Articles
[Zhang S.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Jenkins K.A.]‘s Articles
[Fossat M.J.]‘s Articles
[Zhang S.]‘s Articles
Related Copyright Policies
Null
收藏/分享
所有评论 (0)
暂无评论
 

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.