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典型文献
The parallel tetrameric DNA G-quadruplex formed by the two-repeat C9orf72 GGGGCC sequence in solution
文献摘要:
The abnormal expansion of G-rich hexanucleotide repeat,GGGGCC(G4C2),in chromo-some 9 open reading frame 72(C9orf72)is known to be the prevailing genetic cause of two fatal degenerative neurological diseases,amyotrophic lateral sclerosis(ALS)and fronto-temporal dementia(FTD).It is well known that the DNA G4C2 repeat expansion with different lengths can form G-quadruplexes which affect gene transcription related to ALS/FTD,therefore it is crucial to understand DNA G4C2 G-quadruplex structures.Herein,by utilizing nuclear magnetic resonance(NMR)spectroscopy,we examined DNA G-quad-ruplex structure adopted by two G4C2 hexanucleotide repeats with an inosine substitution at position 4,d(G4C2)2-I4.We show that d(G4C2)2-I4 folds into an eight-layer parallel tetrameric G-quadruplex containing two parallel dimeric G-quadruplexes stacking together through π-π interaction via 5'-to-5'mode in solution.Each dimeric G-quadruplex unit involves two propeller loops composed of two cytosine bases.This result is consistent with the observation in the crystal structure of d(G4C2)2.Our work not only sheds light on the structural diversity of G-quadruplexes adopted by d(G4C2)n but also provides a structural basis for drug design in treatment of ALS and FTD.
文献关键词:
作者姓名:
Changdong Liu;Bo Zhou;Naining Xu;Chun Po Fung;Bing Yan;Monica Ching Suen;Zeguo Huang;Guang Zhu
作者机构:
Division of Life Science,The Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong SAR,00000,China;HKUST Shenzhen Research Institute,Hi-Tech Park,Nanshan,Shenzhen,518057,China;Department of Oral and Maxillofacial Surgery,Stomatological Center,Peking University Shenzhen Hospital,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen,518036,China;Hong Kong Branch of Guangdong Southern Marine Science and Engineering Laboratory(Guangzhou),Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong SAR,00000,China;State Key Laboratory of Molecular Neuroscience,The Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong SAR,00000,China
引用格式:
[1]Changdong Liu;Bo Zhou;Naining Xu;Chun Po Fung;Bing Yan;Monica Ching Suen;Zeguo Huang;Guang Zhu-.The parallel tetrameric DNA G-quadruplex formed by the two-repeat C9orf72 GGGGCC sequence in solution)[J].磁共振快报(英文),2022(04):196-204
A类:
tetrameric,GGGGCC,hexanucleotide,G4C2,ruplex
B类:
parallel,formed,by,two,C9orf72,sequence,solution,abnormal,expansion,rich,chromo,some,open,reading,frame,known,be,prevailing,genetic,cause,fatal,degenerative,neurological,diseases,amyotrophic,lateral,sclerosis,ALS,fronto,temporal,dementia,FTD,It,well,that,different,lengths,can,quadruplexes,which,affect,transcription,related,therefore,crucial,understand,structures,Herein,utilizing,nuclear,magnetic,resonance,NMR,spectroscopy,examined,adopted,repeats,inosine,substitution,position,I4,We,show,folds,into,eight,layer,containing,dimeric,stacking,together,through,interaction,via,mode,Each,unit,involves,propeller,loops,composed,cytosine,bases,This,result,consistent,observation,crystal,Our,work,not,only,sheds,light,structural,diversity,but,also,provides,basis,drug,design,treatment
AB值:
0.523251
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