气候变化领域集成服务门户(CCPortal): A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family

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DOI	10.1073/pnas.2019571118
	A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family
	Jain R.; Muneeruddin K.; Anderson J.; Harms M.J.; Shaffer S.A.; Robert Matthews C.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	The amino acid sequences of proteins have evolved over billions of years, preserving their structures and functions while responding to evolutionary forces. Are there conserved sequence and structural elements that preserve the protein folding mechanisms? The functionally diverse and ancient (βα)1–8 TIM barrel motif may answer this question. We mapped the complex six-state folding free energy surface of a ∼3.6 billion y old, bacterial indole-3-glycerol phosphate synthase (IGPS) TIM barrel enzyme by equilibrium and kinetic hydrogen–deuterium exchange mass spectrometry (HDX-MS). HDX-MS on the intact protein reported exchange in the native basin and the presence of two thermodynamically distinct on- and off-pathway intermediates in slow but dynamic equilibrium with each other. Pro-teolysis revealed protection in a small (α1β2) and a large cluster (β5α5β6α6β7) and that these clusters form cores of stability in Ia and Ibp. The strongest protection in both states resides in β4α4 with the highest density of branched aliphatic side chain contacts in the folded structure. Similar correlations were observed previously for an evolutionarily distinct archaeal IGPS, emphasizing a key role for hydrophobicity in stabilizing common high-energy folding intermediates. A bioinformatics analysis of IGPS sequences from the three superkingdoms revealed an exceedingly high hydrophobicity and surprising α-helix propensity for β4, preceded by a highly conserved βα-hairpin clamp that links β3 and β4. The conservation of the folding mechanisms for archaeal and bacterial IGPS proteins reflects the conservation of key elements of sequence and structure that first appeared in the last universal common ancestor of these ancient proteins. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Hydrogen deuterium exchange; Mass spectrometry; Protein evolution; Protein folding; TIM barrel orthologs
语种	英语
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/179715
作者单位	Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, United States; The Mass Spectrometry Facility, University of Massachusetts Medical School, Shrewsbury, MA 01545, United States; Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR 97403, United States
推荐引用方式 GB/T 7714	Jain R.,Muneeruddin K.,Anderson J.,et al. A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family[J],2021,118(17).
APA	Jain R.,Muneeruddin K.,Anderson J.,Harms M.J.,Shaffer S.A.,&Robert Matthews C..(2021).A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Jain R.,et al."A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).