Abstract:
:Hsp70s use ATP hydrolysis to disrupt protein-protein associations and to move macromolecules. One example is the Hsc70- mediated disassembly of the clathrin coats that form on vesicles during endocytosis. Here, we exploited the exceptional features of these coats to test three models-Brownian ratchet, power-stroke and entropic pulling-proposed to explain how Hsp70s transform their substrates. Our data rule out the ratchet and power-stroke models and instead support a collision-pressure mechanism whereby collisions between clathrin-coat walls and Hsc70s drive coats apart. Collision pressure is the complement to the pulling force described in the entropic pulling model. We also found that self-association augments collision pressure, thereby allowing disassembly of clathrin lattices that have been predicted to be resistant to disassembly. These results illuminate how Hsp70s generate the forces that transform their substrates.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Sousa R,Liao HS,Cuéllar J,Jin S,Valpuesta JM,Jin AJ,Lafer EMdoi
10.1038/nsmb.3272subject
Has Abstractpub_date
2016-09-01 00:00:00pages
821-9issue
9eissn
1545-9993issn
1545-9985pii
nsmb.3272journal_volume
23pub_type
杂志文章abstract::Beta-2 microglobulin (beta2m) is a globular protein that self-associates into fibrillar amyloid deposits in patients undergoing hemodialysis therapy. Formation of these beta-sheet-rich assemblies is a fundamental property of polypeptides that can be triggered by diverse conditions. For beta2m, oligomerization into pre...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1483
更新日期:2008-09-01 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::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/s41594-019-0272-4
更新日期:2019-08-01 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
abstract::Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not b...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1178
更新日期:2006-12-01 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::MicroRNAs (miRNAs) interact with target sites located in the 3' untranslated regions (3' UTRs) of mRNAs to downregulate their expression when the appropriate miRNA is bound to target mRNA. To establish the functional importance of target-site localization in the 3' UTR, we modified the stop codon to extend the coding ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1552
更新日期:2009-02-01 00:00:00
abstract::We developed a 'computational second-site suppressor' strategy to redesign specificity at a protein-protein interface and applied it to create new specifically interacting DNase-inhibitor protein pairs. We demonstrate that the designed switch in specificity holds in in vitro binding and functional assays. We also show...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb749
更新日期:2004-04-01 00:00:00
abstract::During homologous recombination, Rad51 forms a nucleoprotein filament with single-stranded DNA (ssDNA) that undergoes strand exchange with homologous double-stranded DNA (dsDNA). Here, we use real-time analysis to show that strand exchange by fission yeast Rad51 proceeds via two distinct three-strand intermediates, C1...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-017-0002-8
更新日期:2018-01-01 00:00:00
abstract::An increasing body of evidence indicates that transcription and splicing are coupled, and it is accepted that chromatin organization regulates transcription. Little is known about the cross-talk between chromatin structure and exon-intron architecture. By analysis of genome-wide nucleosome-positioning data sets from h...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1659
更新日期:2009-09-01 00:00:00
abstract::To catalyze pre-mRNA splicing, U6 small nuclear RNA positions two metals that interact directly with the scissile phosphates. U6 metal ligands correspond stereospecifically to metal ligands within the catalytic domain V of a group II self-splicing intron. Domain V ligands are organized by base-triple interactions, whi...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2815
更新日期:2014-05-01 00:00:00
abstract::The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes. The N-degrons of type 1 substrates contain an N-terminal basic residue that is recognized by the UBR box domain of the E3...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1907
更新日期:2010-10-01 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::Natural chromosome ends resemble double-stranded DNA breaks, but they do not activate a damage response in healthy cells. Telomeres therefore have evolved to solve the 'end-protection problem' by inhibiting multiple DNA damage-response pathways. During the past decade, the view of telomeres has progressed from simple ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章,评审
doi:10.1038/nsmb.3092
更新日期:2015-11-01 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::Cells respond to changes in environmental conditions via orchestrated modifications in gene expression. For example, in response to heat shock, cells execute a program of gene-specific transcriptional activation and repression. Although the activation of genes upon heat shock has been widely studied, the mechanism of ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb813
更新日期:2004-09-01 00:00:00
abstract::The discovery of the three eukaryotic nuclear RNA polymerases paved the way for serious biochemical investigations of eukaryotic transcription and the identification of eukaryotic transcription factors. Here we describe this adventure from our vantage point, with a focus on the hunt for factors that regulate elongatio...
journal_title:Nature structural & molecular biology
pub_type: 历史文章,杂志文章,评审
doi:10.1038/s41594-019-0283-1
更新日期:2019-09-01 00:00:00
abstract::The ability of barrier-to-autointegration factor (BAF) to bind and bridge DNA in a sequence-independent manner is crucial for its role in retroviral integration and a variety of cellular processes. To better understand this behavior, we solved the crystal structure of BAF bound to DNA. The structure reveals that BAF b...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb989
更新日期:2005-10-01 00:00:00
abstract::The typical function of kinesins is to transport cargo along microtubules. Binding of ATP to microtubule-attached motile kinesins leads to cargo displacement. To better understand the nature of the conformational changes that lead to the power stroke that moves a kinesin's load along a microtubule, we determined the X...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2624
更新日期:2013-08-01 00:00:00
abstract::Although R loops can occur at different genomic locations, the factors that determine their formation and frequency remain unclear. Emerging evidence indicates that DNA breaks stimulate DNA-RNA hybrid formation. Here, we discuss the possibility that formation of hybrids may be an inevitable risk of DNA breaks that occ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3395
更新日期:2017-05-04 00:00:00
abstract::Ribosome-associated quality control (RQC) represents a rescue pathway in eukaryotic cells that is triggered upon translational stalling. Collided ribosomes are recognized for subsequent dissociation followed by degradation of nascent peptides. However, endogenous RQC-inducing sequences and the mechanism underlying the...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-020-0393-9
更新日期:2020-04-01 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::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::Thylakoid assembly 8 (THA8) is a pentatricopeptide repeat (PPR) RNA-binding protein required for the splicing of the transcript of ycf3, a gene involved in chloroplast thylakoid-membrane biogenesis. Here we report the identification of multiple THA8-binding sites in the ycf3 intron and present crystal structures of Br...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2710
更新日期:2013-12-01 00:00:00
abstract::Human telomeres are associated with ATM and the protein complex consisting of MRE11, RAD50 and NBS1 (MRN), which are central to maintaining genomic stability. Here we show that when targeted to telomeres, wild-type RAD50 downregulates telomeric association of TRF1, a negative regulator of telomere maintenance. TRF1 bi...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1286
更新日期:2007-09-01 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::Synaptic transmission relies on an exquisitely orchestrated series of protein-protein interactions. Here we show that fusion driven by neuronal SNAREs is inhibited by the regulatory protein complexin. Furthermore, inner-leaflet mixing is strongly impaired relative to total lipid mixing, indicating that inhibition by c...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1124
更新日期:2006-08-01 00:00:00
abstract::The Rbfox family of splicing factors regulate alternative splicing during animal development and in disease, impacting thousands of exons in the maturing brain, heart and muscle. Rbfox proteins have long been known to bind to the RNA sequence GCAUG with high affinity and specificity, but just half of Rbfox binding sit...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-020-0475-8
更新日期:2020-10-01 00:00:00
abstract::The extracellular domain of the metabotropic glutamate receptor 1alpha (mGluR1alpha) forms a dimer and the ligand, glutamate, induces a structural rearrangement in this domain. However, the conformational change in the cytoplasmic domain, which is critical for mGluR1alpha's interaction with G proteins, remains unclear...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb770
更新日期:2004-07-01 00:00:00