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DOI	10.1073/pnas.1807379115
	The consequences of cavity creation on the folding landscape of a repeat protein depend upon context
	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.
发表日期	2018
ISSN	0027-8424
起始页码	E8153
结束页码	E8161
卷号	115 期号:35
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.
英文关键词	Cooperativity; High pressure; NMR; Repeat protein folding; SAXS
语种	英语
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
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160474
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 Sta...
推荐引用方式 GB/T 7714	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],2018,115(35).
APA	Jenkins K.A..,Fossat M.J..,Zhang S..,Rai D.K..,Klein S..,...&Royer C.A..(2018).The consequences of cavity creation on the folding landscape of a repeat protein depend upon context.Proceedings of the National Academy of Sciences of the United States of America,115(35).
MLA	Jenkins K.A.,et al."The consequences of cavity creation on the folding landscape of a repeat protein depend upon context".Proceedings of the National Academy of Sciences of the United States of America 115.35(2018).