Abstract:
:Catalysis by members of the RNase H superfamily of enzymes is generally believed to require only two Mg2+ ions that are coordinated by active-site carboxylates. By examining the catalytic process of Bacillus halodurans RNase H1 in crystallo, however, we found that the two canonical Mg2+ ions and an additional K+ failed to align the nucleophilic water for RNA cleavage. Substrate alignment and product formation required a second K+ and a third Mg2+, which replaced the first K+ and departed immediately after cleavage. A third transient Mg2+ has also been observed for DNA synthesis, but in that case it coordinates the leaving group instead of the nucleophile as in the case of the RNase H1 hydrolysis reaction. These transient cations have no contact with the enzymes. Other DNA and RNA enzymes that catalyze consecutive cleavage and strand-transfer reactions in a single active site may similarly require cation trafficking coordinated by the substrate.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Samara NL,Yang Wdoi
10.1038/s41594-018-0099-4subject
Has Abstractpub_date
2018-08-01 00:00:00pages
715-721issue
8eissn
1545-9993issn
1545-9985pii
10.1038/s41594-018-0099-4journal_volume
25pub_type
杂志文章abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature structural & molecular biology
pub_type: 已发布勘误
doi:10.1038/s41594-020-0498-1
更新日期:2020-09-01 00:00:00
abstract::The exon-junction complex (EJC) functionally links splicing to subsequent mRNA localization, translation and stability. Sequence-independent binding of the EJC core to RNA is ensured by the DEAD-box helicase eIF4AIII. Here, we identified the splicing factor CWC22 as a new eIF4AIII partner in flies and humans. CWC22 co...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2380
更新日期:2012-10-01 00:00:00
abstract::Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1793
更新日期:2010-04-01 00:00:00
abstract::The eukaryotic exosome is a multisubunit complex typically composed of a catalytically inactive core and the Rrp44 protein, which contains 3'-to-5' exo- and endo-RNase activities. RNA substrates have been shown to be recruited through the core to reach Rrp44's exo-RNase (EXO) site. Using single-particle EM and biochem...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2736
更新日期:2014-01-01 00:00:00
abstract::No-go decay (NGD) targets mRNAs with stalls in translation elongation for endonucleolytic cleavage in a process involving the Dom34 and Hbs1 proteins. The crystal structure of a Schizosaccharomyces pombe Dom34-Hbs1 complex reveals an overall shape similar to that of eRF1-eRF3-GTP and EF-Tu-tRNA-GDPNP. Similarly to eRF...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1922
更新日期:2010-10-01 00:00:00
abstract::The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs undergoing premature termination of translation. It has been argued that in human cells, NMD is restricted to a pioneer round of translation initiated on mRNAs associated with the cap-binding complex (CBC) and that the exchange of the CBC for the eIF4F tran...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2575
更新日期:2013-06-01 00:00:00
abstract::The tandem zinc finger (TZF) domain of the protein TIS11d binds to the class II AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and promotes their deadenylation and degradation. The NMR structure of the TIS11d TZF domain bound to the RNA sequence 5'-UUAUUUAUU-3' comprises a pair of novel C...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb738
更新日期:2004-03-01 00:00:00
abstract::Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates wi...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2615
更新日期:2013-07-01 00:00:00
abstract::RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome wide in mouse and human cells, and it is required to limit enhancer-RNA initiation and synthesis in a ma...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3176
更新日期:2016-03-01 00:00:00
abstract::The spliceosome is thought to undergo a conformational change between the two catalytic steps of precursor messenger RNA splicing, although the specific events in this transition are poorly understood. We previously proposed a two-state model of splicing in which the conformations required for the first and second ste...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1240
更新日期:2007-06-01 00:00:00
abstract::The cyclic enzymatic removal and ligation of the C-terminal tyrosine of α-tubulin generates heterogeneous microtubules and affects their functions. Here we describe the crystal and solution structure of the tubulin carboxypeptidase complex between vasohibin (VASH1) and small vasohibin-binding protein (SVBP), which fol...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0254-6
更新日期:2019-07-01 00:00:00
abstract::The interaction of autotaxin with its substrates leads to the production of lysophosphatidic acids (LPA), bioactive lipids with an emerging prominent role in inflammation and cancer. Two papers in this issue tell the previously unknown story of autotaxin, from substrate discrimination to highly efficient local deliver...
journal_title:Nature structural & molecular biology
pub_type: 评论,杂志文章
doi:10.1038/nsmb0211-117
更新日期:2011-02-01 00:00:00
abstract::Obesity and type II diabetes are closely linked metabolic syndromes that afflict >100 million people worldwide. Although protein tyrosine phosphatase 1B (PTP1B) has emerged as a promising target for the treatment of both syndromes, the discovery of pharmaceutically acceptable inhibitors that bind at the active site re...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb803
更新日期:2004-08-01 00:00:00
abstract::Flavin-containing monooxygenases (FMOs) are ubiquitous in all domains of life and metabolize a myriad of xenobiotics, including toxins, pesticides and drugs. However, despite their pharmacological importance, structural information remains bereft. To further our understanding behind their biochemistry and diversity, w...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0347-2
更新日期:2020-01-01 00:00:00
abstract::Lipoteichoic acids (LTAs) are essential cell-wall components in Gram-positive bacteria, including the human pathogen Staphylococcus aureus, contributing to cell adhesion, cell division and antibiotic resistance. Genetic evidence has suggested that LtaA is the flippase that mediates the translocation of the lipid-linke...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-020-0425-5
更新日期:2020-06-01 00:00:00
abstract::Biogenesis of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits, requires assembly chaperones. Here we analyzed the role of Rubisco accumulation factor1 (Raf1), a dimer of ∼40-kDa subunits. We find that Raf1 from Synechococcus elongatus acts downstream of chaperonin-ass...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3062
更新日期:2015-09-01 00:00:00
abstract::The Saccharomyces cerevisiae proteasome comprises a 19-subunit regulatory particle and a 28-subunit core particle. To be degraded, substrates must cross the core particle-regulatory particle interface, a site for complex conformational changes and regulatory events. This interface includes two aligned heteromeric ring...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2147
更新日期:2011-10-30 00:00:00
abstract::The general preprotein translocase of the outer mitochondrial membrane (TOM complex) transports virtually all mitochondrial precursor proteins, but cannot assemble outer-membrane precursors into functional complexes. A recently discovered sorting and assembly machinery (SAM complex) is essential for integration and as...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章,评审
doi:10.1038/nsmb852
更新日期:2004-11-01 00:00:00
abstract::Many aspects of nucleic acid metabolism, such as DNA replication, repair and transcription, are regulated by the post-translational modifiers ubiquitin and SUMO. Not surprisingly, DNA itself plays an integral part in determining the modification of most chromatin-associated targets. Conversely, ubiquitination or SUMOy...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章,评审
doi:10.1038/nsmb.2805
更新日期:2014-04-01 00:00:00
abstract::We have isolated a soluble cytochrome from Shewanella oneidensis that contains eight covalently attached heme groups and determined its crystal structure. One of these hemes exhibits novel ligation of the iron atom by the epsilon-amino group of a lysine residue, despite its attachment via a typical CXXCH motif. This h...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb827
更新日期:2004-10-01 00:00:00
abstract::Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, re...
journal_title:Nature structural & molecular biology
pub_type: 评论,新闻
doi:10.1038/nsmb.2620
更新日期:2013-07-01 00:00:00
abstract::The cocrystal structure of the PP7 bacteriophage coat protein in complex with its translational operator identifies a distinct mode of sequence-specific RNA recognition when compared to the well-characterized MS2 coat protein-RNA complex. The structure reveals the molecular basis of the PP7 coat protein's ability to s...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1327
更新日期:2008-01-01 00:00:00
abstract::Maintenance of cell volume against osmotic change is crucial for proper cell functions. Leucine-rich repeat-containing 8 proteins are anion-selective channels that extrude anions to decrease the cell volume on cellular swelling. Here, we present the structure of human leucine-rich repeat-containing 8A, determined by s...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-018-0109-6
更新日期:2018-09-01 00:00:00
abstract::Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repe...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1629
更新日期:2009-07-01 00:00:00
abstract::Podovirus P-SSP7 infects Prochlorococcus marinus, the most abundant oceanic photosynthetic microorganism. Single-particle cryo-electron microscopy yields icosahedral and asymmetrical structures of infectious P-SSP7 with 4.6-A and 9-A resolution, respectively. The asymmetric reconstruction reveals how symmetry mismatch...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1823
更新日期:2010-07-01 00:00:00
abstract::Here we report the crystal structures of I.C and I.A wobble base pairs in the context of the ribosomal decoding center, clearly showing that the I.A base pair is of an I(anti).A(anti) conformation, as predicted by Crick. Additionally, the structures enable the observation of changes in the anticodon to allow purine-pu...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb866
更新日期:2004-12-01 00:00:00
abstract::Aquaporin (AQP) folding in the endoplasmic reticulum is characterized by two distinct pathways of membrane insertion that arise from divergent residues within the second transmembrane segment. We now show that in AQP1 these residues (Asn49 and Lys51) interact with Asp185 at the C terminus of TM5 to form a polar, quate...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1275
更新日期:2007-08-01 00:00:00
abstract::A fundamental question is how enzymes can accelerate chemical reactions. Catalysis is not only defined by actual chemical steps, but also by enzyme structure and dynamics. To investigate the role of protein dynamics in enzymatic turnover, we measured residue-specific protein dynamics in hyperthermophilic and mesophili...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb821
更新日期:2004-10-01 00:00:00
abstract::Proteins regulate gene expression by controlling mRNA biogenesis, localization, translation and decay. Identifying the composition, diversity and function of mRNA-protein complexes (mRNPs) is essential to understanding these processes. In a global survey of Saccharomyces cerevisiae mRNA-binding proteins, we identified...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2468
更新日期:2013-01-01 00:00:00
abstract::Otopetrins (Otop1-Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architectur...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0235-9
更新日期:2019-06-01 00:00:00