Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine

被引:412
作者
Batey, RT [1 ]
Gilbert, SD [1 ]
Montange, RK [1 ]
机构
[1] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA
关键词
D O I
10.1038/nature03037
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Riboswitches are genetic regulatory elements found in the 50 untranslated region of messenger RNA that act in the absence of protein cofactors(1,2). They are broadly distributed across bacteria and account for the regulation of more than 2% of all genes in Bacillus subtilis, underscoring their importance in the control of cellular metabolism(3). The 5' untranslated region of many mRNAs of genes involved in purine metabolism and transport contain a guanine-responsive riboswitch that directly binds guanine, hypoxanthine or xanthine to terminate transcription(3,4). Here we report the crystal structure at 1.95 Angstrom resolution of the purine-binding domain of the guanine riboswitch from the xpt-pbuX operon of B. subtilis bound to hypoxanthine, a prevalent metabolite in the bacterial purine salvage pathway. This structure reveals a complex RNA fold involving several phylogenetically conserved nucleotides that create a binding pocket that almost completely envelops the ligand. Hypoxanthine functions to stabilize this structure and to promote the formation of a downstream transcriptional terminator element, thereby providing a mechanism for directly repressing gene expression in response to an increase in intracellular concentrations of metabolite.
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页码:411 / 415
页数:5
相关论文
共 28 条
[1]   2.8 Å crystal structure of the malachite green aptamer [J].
Baugh, C ;
Grate, D ;
Wilson, C .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 301 (01) :117-128
[2]  
Brunger AT, 1998, ACTA CRYSTALLOGR D, V54, P905, DOI 10.1107/s0907444998003254
[3]   Crystal structure of a group I ribozyme domain: Principles of RNA packing [J].
Cate, JH ;
Gooding, AR ;
Podell, E ;
Zhou, KH ;
Golden, BL ;
Kundrot, CE ;
Cech, TR ;
Doudna, JA .
SCIENCE, 1996, 273 (5282) :1678-1685
[4]   STRUCTURAL CHARACTERIZATION AND COREPRESSOR BINDING OF THE ESCHERICHIA-COLI PURINE REPRESSOR [J].
CHOI, KY ;
ZALKIN, H .
JOURNAL OF BACTERIOLOGY, 1992, 174 (19) :6207-6214
[5]   The common and the distinctive features of the bulged-G motif based on a 1.04 Å resolution RNA structure [J].
Correll, CC ;
Beneken, J ;
Plantinga, MJ ;
Lubbers, M ;
Chan, YL .
NUCLEIC ACIDS RESEARCH, 2003, 31 (23) :6806-6818
[6]   Peripheral regions of natural hammerhead ribozymes greatly increase their self-cleavage activity [J].
De la Peña, M ;
Gago, S ;
Flores, R .
EMBO JOURNAL, 2003, 22 (20) :5561-5570
[7]   A universal mode of helix packing in RNA [J].
Doherty, EA ;
Batey, RT ;
Masquida, B ;
Doudna, JA .
NATURE STRUCTURAL BIOLOGY, 2001, 8 (04) :339-343
[8]   INVITRO SELECTION OF RNA MOLECULES THAT BIND SPECIFIC LIGANDS [J].
ELLINGTON, AD ;
SZOSTAK, JW .
NATURE, 1990, 346 (6287) :818-822
[9]   Molecular recognition in the FMN-RNA aptamer complex [J].
Fan, P ;
Suri, AK ;
Fiala, R ;
Live, D ;
Patel, DJ .
JOURNAL OF MOLECULAR BIOLOGY, 1996, 258 (03) :480-500
[10]   DIVERSITY OF OLIGONUCLEOTIDE FUNCTIONS [J].
GOLD, L ;
POLISKY, B ;
UHLENBECK, O ;
YARUS, M .
ANNUAL REVIEW OF BIOCHEMISTRY, 1995, 64 :763-797