Abstract:
:The regulated exocytotic release of neurotransmitter and hormones is accomplished by a complex protein machinery whose core consists of SNARE proteins and the calcium sensor synaptotagmin-1. We propose a mechanism in which the lipid membrane is intimately involved in coupling calcium sensing to release. We found that fusion of dense core vesicles, derived from rat PC12 cells, was strongly linked to the angle between the cytoplasmic domain of the SNARE complex and the plane of the target membrane. We propose that, as this tilt angle increases, force is exerted on the SNARE transmembrane domains to drive the merger of the two bilayers. The tilt angle markedly increased following calcium-mediated binding of synaptotagmin to membranes, strongly depended on the surface electrostatics of the membrane, and was strictly coupled to the lipid order of the target membrane.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Kiessling V,Kreutzberger AJB,Liang B,Nyenhuis SB,Seelheim P,Castle JD,Cafiso DS,Tamm LKdoi
10.1038/s41594-018-0130-9subject
Has Abstractpub_date
2018-10-01 00:00:00pages
911-917issue
10eissn
1545-9993issn
1545-9985pii
10.1038/s41594-018-0130-9journal_volume
25pub_type
杂志文章abstract::Pre-messenger RNAs (pre-mRNAs) maturation is initiated cotranscriptionally. It is therefore conceivable that chromatin-borne information participates in alternative splicing. Here we find that elevated levels of trimethylation of histone H3 on Lys9 (H3K9me3) are a characteristic of the alternative exons of several gen...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1995
更新日期:2011-03-01 00:00:00
abstract:: ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-018-0167-9
更新日期:2018-12-01 00:00:00
abstract::P element transposase catalyzes the mobility of P element DNA transposons within the Drosophila genome. P element transposase exhibits several unique properties, including the requirement for a guanosine triphosphate cofactor and the generation of long staggered DNA breaks during transposition. To gain insights into t...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0319-6
更新日期:2019-11-01 00:00:00
abstract::Although the two B-family human DNA polymerases, pol δ and pol ε, are responsible for the bulk of nuclear genome replication, at least 14 additional polymerases have roles in nuclear DNA repair and replication. In this issue, newly reported crystal structures of two specialized A-family polymerases, pol δ and pol ε, e...
journal_title:Nature structural & molecular biology
pub_type: 评论,杂志文章
doi:10.1038/nsmb.3006
更新日期:2015-04-01 00:00:00
abstract::To our knowledge, no structural study to date has characterized, in an intact receptor, the coupling of conformational change in extracellular domains through a single-pass transmembrane domain to conformational change in cytoplasmic domains. Here we examine such coupling, and its unexpected complexity, using nearly f...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2092
更新日期:2011-08-07 00:00:00
abstract::Messenger RNAs produced by splicing are translated more efficiently than those produced from similar intronless precursor mRNAs (pre-mRNAs). The exon-junction complex (EJC) probably mediates this enhancement; however, the specific link between the EJC and the translation machinery has not been identified. The EJC prot...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1321
更新日期:2007-12-01 00:00:00
abstract::To determine which genomic features promote homologous recombination, we created a genome-wide map of gene targeting sites. We used an adeno-associated virus vector to target identical loci introduced as transcriptionally active retroviral vectors. A comparison of ~2,000 targeted and untargeted sites showed that targe...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2895
更新日期:2014-11-01 00:00:00
abstract::The computational design of α-helical membrane proteins is still in its infancy but has already made great progress. De novo design allows stable, specific and active minimal oligomeric systems to be obtained. Computational reengineering can improve the stability and function of naturally occurring membrane proteins. ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3231
更新日期:2016-06-07 00:00:00
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::Histone H3 Lys4 (H3K4) methylation is a prevalent mark associated with transcription activation. A common feature of several H3K4 methyltransferase complexes is the presence of three structural components (RbBP5, Ash2L and WDR5) and a catalytic subunit containing a SET domain. Here we report the first biochemical reco...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1128
更新日期:2006-08-01 00:00:00
abstract::The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positions. ISWI regulates nucleosome positioning by requiring a minimal length of extranucleosomal DNA for moving nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain cal...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2486
更新日期:2013-02-01 00:00:00
abstract::The potassium channel selectivity filter both discriminates between K(+) and sodium ions and contributes to gating of ion flow. Static structures of conducting (open) and nonconducting (inactivated) conformations of this filter are known; however, the sequence of protein rearrangements that connect these two states is...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1966
更新日期:2011-01-01 00:00:00
abstract::Mg-ADP release is considered to be a crucial process for the regulation and motility of kinesin. To gain insight into the structural basis of this process, we solved the atomic structures of kinesin superfamily protein-1A (KIF1A) during and after Mg(2+) release. On the basis of new structural and mutagenesis data, we ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1487
更新日期:2008-10-01 00:00:00
abstract:: ...
journal_title:Nature structural & molecular biology
pub_type: 评论,信件
doi:10.1038/s41594-018-0145-2
更新日期:2018-11-01 00:00:00
abstract::Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however, AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antib...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3048
更新日期:2015-07-01 00:00:00
abstract::The proteasome is the main ATP-dependent protease in eukaryotic cells and controls the concentration of many regulatory proteins in the cytosol and nucleus. Proteins are targeted to the proteasome by the covalent attachment of polyubiquitin chains. The ubiquitin modification serves as the proteasome recognition elemen...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb814
更新日期:2004-09-01 00:00:00
abstract::Gene expression is inherently stochastic; precise gene regulation by transcription factors is important for cell-fate determination. Many transcription factors regulate their own expression, suggesting that autoregulation counters intrinsic stochasticity in gene expression. Using a new strategy, cotranslational activa...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2336
更新日期:2012-08-01 00:00:00
abstract::Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-018-0123-8
更新日期:2018-09-01 00:00:00
abstract::STING functions as both an adaptor protein signaling cytoplasmic double-stranded DNA and a direct immunosensor of cyclic diguanylate monophosphate (c-di-GMP). The crystal structures of the C-terminal domain of human STING (STING(CTD)) and its complex with c-di-GMP reveal how STING recognizes c-di-GMP. In response to c...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2332
更新日期:2012-06-24 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::Kinases are involved in disease development and modulation of their activity can be therapeutically beneficial. Drug-resistant mutant kinases are valuable tools in drug discovery efforts, but the prediction of mutants across the kinome is challenging. Here, we generate deep mutational scanning data to identify mutant ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0358-z
更新日期:2020-01-01 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::Bacteriophages express proteins that inactivate the CRISPR-Cas bacterial immune system. Here we report the crystal structure of the anti-CRISPR protein AcrF3 in complex with Pseudomonas aeruginosa Cas3 (PaCas3). AcrF3 forms a homodimer that locks PaCas3 in an ADP-bound form, blocks the entrance of the DNA-binding tunn...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3269
更新日期:2016-09-01 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::The GTPase dynamin is essential for numerous vesiculation events including clathrin-mediated endocytosis. Upon GTP hydrolysis, dynamin constricts a lipid bilayer. Previously, a three-dimensional structure of mutant dynamin in the constricted state was determined by helical reconstruction methods. We solved the noncons...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb762
更新日期:2004-06-01 00:00:00
abstract::Spliceosomes catalyze the maturation of precursor mRNAs in organisms ranging from yeast to humans. Their catalytic core comprises three small nuclear RNAs (U2, U5 and U6) involved in substrate positioning and catalysis. It has been postulated, but never shown experimentally, that the U2-U6 complex adopts at least two ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1672
更新日期:2009-11-01 00:00:00
abstract::Bacteriophage T4 and related viruses have a contractile tail that serves as an efficient mechanical device for infecting bacteria. A three-dimensional cryo-EM reconstruction of the mature T4 tail assembly at 15-A resolution shows the hexagonal dome-shaped baseplate, the extended contractile sheath, the long tail fiber...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb975
更新日期:2005-09-01 00:00:00
abstract::In eukaryotic cells, many introns are constitutively, rather than alternatively, spliced and therefore do not contribute to isoform diversification. It has remained unclear what functional roles such constitutive splicing provides. To explore this issue, we asked how splicing affects the efficiency with which individu...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-019-0226-x
更新日期:2019-06-01 00:00:00
abstract::It has recently been shown that RNA 3'-end formation plays a more widespread role in controlling gene expression than previously thought. To examine the impact of regulated 3'-end formation genome-wide, we applied direct RNA sequencing to A. thaliana. Here we show the authentic transcriptome in unprecedented detail an...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2345
更新日期:2012-08-01 00:00:00
abstract::We present the first large-scale identification of lariats-the transient branched introns that are released as a byproduct of pre-mRNA splicing. The locations of the branchpoints in these introns provide insight into the early steps of splicing. From this data set, we have developed a comprehensive model of 3' splice-...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2327
更新日期:2012-06-17 00:00:00