气候变化领域集成服务门户(CCPortal): Helicase-like functions in phosphate loop containing beta-alpha polypeptides

CCPortal

DOI	10.1073/pnas.2016131118
	Helicase-like functions in phosphate loop containing beta-alpha polypeptides
	Vyas P.; Trofimyuk O.; Longo L.M.; Deshmukh F.K.; Sharon M.; Tawfik D.S.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	The P-loop Walker A motif underlies hundreds of essential enzyme families that bind nucleotide triphosphates (NTPs) and mediate phosphoryl transfer (P-loop NTPases), including the earliest DNA/ RNA helicases, translocases, and recombinases. What were the primordial precursors of these enzymes? Could these large and complex proteins emerge from simple polypeptides? Previously, we showed that P-loops embedded in simple βα repeat proteins bind NTPs but also, unexpectedly so, ssDNA and RNA. Here, we extend beyond the purely biophysical function of ligand binding to demonstrate rudimentary helicase-like activities. We further constructed simple 40-residue polypeptides comprising just one β-(P-loop)-α element. Despite their simplicity, these P-loop prototypes confer functions such as strand separation and exchange. Foremost, these polypeptides unwind dsDNA, and upon addition of NTPs, or inorganic polyphosphates, release the bound ssDNA strands to allow reformation of dsDNA. Binding kinetics and low-resolution structural analyses indicate that activity is mediated by oligomeric forms spanning from dimers to high-order assemblies. The latter are reminiscent of extant P-loop recombinases such as RecA. Overall, these P-loop prototypes compose a plausible description of the sequence, structure, and function of the earliest P-loop NTPases. They also indicate that multifunctionality and dynamic assembly were key in endowing short polypeptides with elaborate, evolutionarily relevant functions. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Multifunctionality; P-loop; Polyphosphate; Protein evolution; Walker A
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/179847
作者单位	Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel; Tokyo Institute of Technology, Earth-Life Science Institute, Tokyo, 152-8550, Japan; Blue Marble Space Institute of Science, Seattle, WA 98104, United States
推荐引用方式 GB/T 7714	Vyas P.,Trofimyuk O.,Longo L.M.,et al. Helicase-like functions in phosphate loop containing beta-alpha polypeptides[J],2021,118(16).
APA	Vyas P.,Trofimyuk O.,Longo L.M.,Deshmukh F.K.,Sharon M.,&Tawfik D.S..(2021).Helicase-like functions in phosphate loop containing beta-alpha polypeptides.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Vyas P.,et al."Helicase-like functions in phosphate loop containing beta-alpha polypeptides".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).