Abstract：
:The 26S proteasome is the essential compartmental protease in eukaryotic cells required for the ubiquitin-dependent clearance of damaged polypeptides and obsolete regulatory proteins. Recently, a combination of high-resolution structural, biochemical, and biophysical studies has provided crucial new insights into the mechanisms of this fascinating molecular machine. A multitude of new cryo-electron microscopy structures provided snapshots of the proteasome during ATP-hydrolysis-driven substrate translocation, and detailed biochemical studies revealed the timing of individual degradation steps, elucidating the mechanisms for substrate selection and the commitment to degradation through conformational transitions. It was uncovered how ubiquitin removal from substrates is mechanically coupled to degradation, and cryo-electron tomography studies gave a glimpse of active proteasomes inside the cell, their subcellular localization, and interactions with protein aggregates. Here, we summarize these advances in our mechanistic understanding of the proteasome, with a particular focus on how its structural features and conformational transitions enable the multi-step degradation process.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Greene ER,Dong KC,Martin Adoi
10.1016/j.sbi.2019.10.004subject
Has Abstractpub_date
2020-04-01 00:00:00pages
33-41eissn
0959-440Xissn
1879-033Xpii
S0959-440X(19)30114-9journal_volume
61pub_type
杂志文章,评审abstract：:The spliceosome executes eukaryotic precursor messenger RNA (pre-mRNA) splicing to remove noncoding introns through two sequential transesterification reactions, branching and exon ligation. The fidelity of this process is based on the recognition of the conserved sequences in the intron and dynamic compositional and ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2003.10.011
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abstract：:Structures of three different pleckstrin homology domains have been determined within the past year. They have a common core consisting of a seven-stranded and strongly bent beta-sheet and a C-terminal alpha-helix that packs against the beta-sheet. Phosphatidylinositol 4,5-bisphosphate and related compounds specifical...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80104-9
更新日期：1995-06-01 00:00:00
abstract：:Progress in the synthesis, purification and crystallization of RNA has resulted in the determination of several X-ray crystal structures of RNA molecules over the past few years. Methods proven and under development will lead to future structure determinations and shed light on the structural basis for RNA's many func...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80057-3
更新日期：1995-10-01 00:00:00
abstract：:The exponential growth in the amount of genomic data published in recent years has led to increased efforts in analysing genomes for the presence of repeated sequences, which has in turn fostered the development of novel repeat recognition methods. This has resulted in a deepened understanding of the importance and ab...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(98)80068-7
更新日期：1998-06-01 00:00:00
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2004.04.005
更新日期：2004-06-01 00:00:00
abstract：:Understanding the structural rules that govern specific, high-affinity binding characteristic of aptamer-protein interactions is important in view of the increasing use of aptamers across many applications. From the modest number of 16 aptamer-protein structures currently available, trends are emerging. The flexible p...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.01.009
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2007.03.005
更新日期：2007-04-01 00:00:00
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.07.014
更新日期：2016-10-01 00:00:00
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/S0959-440X(99)80035-9
更新日期：1999-04-01 00:00:00
abstract：:Bacterial transcription initiation is controlled by sigma factors, the RNA polymerase (RNAP) subunits responsive for promoter specificity. While the primary sigma factor ensures the bulk of transcription during growth, a major strategy used by bacteria to regulate gene expression consists of modifying the RNAP promote...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2015.01.006
更新日期：2015-02-01 00:00:00
abstract：:Ribonuclease P (RNase P) is one of only two known universal ribozymes and was one of the first ribozymes to be discovered. It is involved in RNA processing, in particular the 5' maturation of tRNA. Unlike most other natural ribozymes, it recognizes and cleaves its substrate in trans. RNase P is a ribonucleoprotein com...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.04.002
更新日期：2006-06-01 00:00:00
abstract：:This review focuses on pharmacophore approaches in researching protein interfaces that bind protein ligands. Pharmacophore descriptions of binding interfaces that employ molecular dynamics simulation can account for effects of solvation and conformational flexibility. In addition, these calculations provide an approxi...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.12.016
更新日期：2021-01-21 00:00:00
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(00)00154-8
更新日期：2000-12-01 00:00:00
abstract：:Purification from a source enriched in large macromolecular machines with basic cellular function is still the method of choice in many cases. Such complexes occur in sufficiently high copy numbers in the cell and can be isolated using classical protein purification protocols. Although advanced DNA recombinant technol...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.01.005
更新日期：2013-06-01 00:00:00
abstract：:Progress in structural biology has begun to reveal the precise architecture of integral membrane proteins. However, the manner in which these complex structures are achieved remains unclear. Recent developments are starting to shed light on the unfolding and folding of a small but growing number of membrane proteins. ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.06.004
更新日期：2006-08-01 00:00:00
abstract：:Structure-specific DNA nucleases play important roles in various DNA transactions such as DNA replication, repair and recombination. These enzymes recognize loops and branched DNA structures. Recent structural studies have provided detailed insights into the functions of these enzymes. Structures of Holliday junction ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.01.009
更新日期：2006-02-01 00:00:00
abstract：:Advances in the crystallization of biological macromolecules have come not only from the application of biochemical, molecular biological and immunological principles and techniques, but also from continued efforts to understand the crystallization process. Developments in crystallization methodologies, protocols, and...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(96)80024-8
更新日期：1996-10-01 00:00:00
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journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.06.011
更新日期：2020-12-01 00:00:00
abstract：:A network of dynamic protein interactions with their protein partners, substrates, and ligands is known to be crucial for biological function. Revealing molecular and structural-based mechanisms at atomic resolution and in real-time is fundamental for achieving a basic understanding of cellular processes. These techni...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.07.008
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abstract：:The recently determined structure of octameric mitochondrial creatine kinase has provided new insights into the functioning of this enzyme and its role in channelling energy from the mitochondria to the cytoplasm. Creatine kinase, a member of the family of guanidino kinases, is structurally similar to glutamine synthe...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80151-0
更新日期：1997-12-01 00:00:00
abstract：:Fundamental biological processes are driven by diverse molecular machineries. In recent years, single-molecule fluorescence spectroscopy has matured as a unique tool in biology to study how structural dynamics of molecular complexes drive various biochemical reactions. In this review, we highlight underlying developme...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.05.005
更新日期：2019-10-01 00:00:00
abstract：:Mass spectrometry is becoming a more and more powerful tool for investigating protein complexes. Recent developments, based on different ionization techniques, electrospray, desorption/ionization and others are contributing to the usefulness of MS to describe the organization and structure of large non-covalent assemb...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2009.08.004
更新日期：2009-10-01 00:00:00
abstract：:Given the increasing interest in protein-protein interactions, the prediction of these interactions from sequence and structural information has become a booming activity. CAPRI, the community-wide experiment for assessing blind predictions of protein-protein interactions, is playing an important role in fostering pro...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2004.02.003
更新日期：2004-04-01 00:00:00
abstract：:Recent advances in ab initio direct methods have enabled the solution of crystal structures of small proteins from native X-ray data alone, that is, without the use of fragments of known structure or the need to prepare heavy-atom or selenomethionine derivatives, provided that the data are available to atomic resoluti...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(99)00020-2
更新日期：1999-10-01 00:00:00
abstract：:The postsynaptic density (PSD) is a protein-rich assembly below the postsynaptic membrane, formed of large scaffolding proteins. These proteins carry a combination of protein interaction domains, which may interact with several alternative partners; the structure of the protein assembly can be regulated in an activity...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.01.007
更新日期：2019-02-01 00:00:00
abstract：:Improved rational drug design methods are needed to lower the cost and increase the success rate of drug discovery and development. Alchemical binding free energy calculations, one potential tool for rational design, have progressed rapidly over the past decade, but still fall short of providing robust tools for pharm...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.01.011
更新日期：2011-04-01 00:00:00
abstract：:Maintenance of telomeres by the enzyme telomerase is essential for genomic stability and cell viability in ciliates, vertebrates and yeast. The minimal components of telomerase required for catalytic activity are the telomerase reverse transcriptase (TERT) protein and the template-containing telomerase RNA (TER). Rece...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.05.005
更新日期：2006-06-01 00:00:00
abstract：:A large body of work has gone into understanding the effect of mutations on protein structure and function. Conventional treatments have involved quantifying the change in stability, activity and relaxation rates of the mutants with respect to the wild-type protein. However, it is now becoming increasingly apparent th...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2018.09.004
更新日期：2019-02-01 00:00:00
