Abstract:
:Advances in electron microscopes, detectors and data processing algorithms have greatly facilitated the structural determination of many challenging integral membrane proteins that have been evasive to crystallization. These breakthroughs facilitate the application and development of various membrane protein solubilization approaches for structural studies, including reconstitution into lipid nanoparticles. In this review, we discuss various approaches for preparing transmembrane proteins for structural determination with single-particle electron cryo microscopy (cryoEM).
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Autzen HE,Julius D,Cheng Ydoi
10.1016/j.sbi.2019.05.022subject
Has Abstractpub_date
2019-10-01 00:00:00pages
259-268eissn
0959-440Xissn
1879-033Xpii
S0959-440X(18)30117-9journal_volume
58pub_type
杂志文章,评审abstract::The 5' m7GpppN cap plays an essential role in the life cycle of eukaryotic mRNA and is required for efficient pre-mRNA splicing, export, stability and translation. Nascent pre-mRNA is capped through a series of three enzymatic steps that result in a 5' N7-methyl guanosine linked by an inverted 5'-5' triphosphate bridg...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2005.01.009
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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
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abstract::Connecting dynamics to structural data from diverse experimental sources, molecular dynamics simulations permit the exploration of biological phenomena in unparalleled detail. Advances in simulations are moving the atomic resolution descriptions of biological systems into the million-to-billion atom regime, in which n...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2015.03.007
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abstract::Protein aggregation constitutes a constant threat for the living cell as is demonstrated by the several pathologies in which the mechanisms to prevent it fail. It is therefore a question of increasing importance to understand in detail the defence strategies. Here we discuss how molecular interactions can represent a ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2011.11.007
更新日期:2012-02-01 00:00:00
abstract::Self-compartmentalizing proteases, such as the proteasome and several prokaryotic energy-dependent proteases, are designed to act in the crowded environment of the cell. Proteins destined for degradation are recognized and unfolded by regulatory subcomplexes that invariably contain ATPase modules, before being translo...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(00)00075-0
更新日期:2000-04-01 00:00:00
abstract::Zinc finger proteins are among the most abundant proteins in eukaryotic genomes. Their functions are extraordinarily diverse and include DNA recognition, RNA packaging, transcriptional activation, regulation of apoptosis, protein folding and assembly, and lipid binding. Zinc finger structures are as diverse as their f...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(00)00167-6
更新日期:2001-02-01 00:00:00
abstract::A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Structural Biology. ...
journal_title:Current opinion in structural biology
pub_type:
doi:10.1016/s0959-440x(00)00182-2
更新日期:2001-04-01 00:00:00
abstract::Viruses with an icosahedrally symmetric protein capsid and a membrane infect hosts from all three domains of life. Similar architectural principles are shared by different viral families, as exemplified by double-stranded DNA viruses such as PRD1 and STIV. During virus assembly, the membrane lipids are selectively acq...
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
abstract::Significant progress has been made over the past several years on structural studies of the eukaryotic translation initiation factors that facilitate the assembly of a translation-competent ribosome at the initiation codon of an mRNA. These structural studies have revealed the repeated use of a set of common structura...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(03)00009-5
更新日期:2003-02-01 00:00:00
abstract::The sema domain was first defined from sequence by Kolodkin and colleagues in the early 1990s, and constitutes the distinctive structural and functional element of semaphorins, their plexin receptors and the receptor tyrosine kinases MET and RON, three protein families with major roles in development, tissue regenerat...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2004.10.010
更新日期:2004-12-01 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::Force spectroscopy has developed into an indispensable tool for studying folding and binding of proteins on a single molecule level in real time. Design of the pulling geometry allows tuning the reaction coordinate in a very precise manner. Many recent experiments have taken advantage of this possibility and have prov...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2012.11.007
更新日期:2013-02-01 00:00:00
abstract::Polyketide synthases (PKSs) form a large family of multifunctional proteins involved in the biosynthesis of diverse classes of natural products. Architecturally at least three different types of PKSs have been discovered in the microbial world and recent years have revealed tremendous versatility of PKSs, both in term...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2007.08.021
更新日期:2007-12-01 00:00:00
abstract::All domains of life make carbohydrate polymers and by anchoring them to lipid molecules they can decorate the outside of the cell. Polysaccharides are linked to proteins by glycosylation, a process found in both bacteria and in higher organisms. Bacteria do have other distinct uses for carbohydrate polymers; in gram-n...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2016.07.016
更新日期:2016-10-01 00:00:00
abstract::Histones are highly positively charged proteins that wrap our genome. Their surface properties also make them prone to nonspecific interactions and aggregation. A class of proteins known as histone chaperones is dedicated to safeguard histones by aiding their proper incorporation into nucleosomes. Histone chaperones f...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2011.10.003
更新日期:2011-12-01 00:00:00
abstract::DNA photolyases are extremely efficient light-driven DNA repair enzymes that use the energy of a blue-light photon to 'inject' an electron onto UV-damaged DNA, catalyzing the splitting of mutagenic pyrimidine dimers. By contrast, cryptochromes use blue light to trigger signaling cascades in multicellular organisms, fu...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2006.01.004
更新日期:2006-02-01 00:00:00
abstract::ATP-dependent initiation factors help process replication origins and coordinate replisome assembly to control the onset of DNA synthesis. Although the specific properties and regulatory mechanisms of initiator proteins can vary greatly between different organisms, certain nucleotide-binding elements and assembly patt...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2012.11.012
更新日期:2013-02-01 00:00:00
abstract::The past decade has seen a revolution in our ability to engineer designer enzymes using genetic tools that mimic evolution on a laboratory timescale. Many excellent examples of directed evolution applied to a wide range of enzymes have clearly demonstrated its future role in adapting enzymes for use in the chemical in...
journal_title:Current opinion in structural biology
pub_type: 杂志文章
doi:10.1016/s0959-440x(03)00101-5
更新日期:2003-08-01 00:00:00
abstract::Since its debut in the mid 1970s, electron crystallography has been a valuable alternative in the structure determination of biological macromolecules. Its reliance on single-layered or double-layered two-dimensionally ordered arrays and the ability to obtain structural information from small and disordered crystals m...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2012.03.006
更新日期:2012-08-01 00:00:00
abstract::The RNA exosome participates in the degradation and processing of a wide range of RNA molecules. Recent advances in understanding how the exosome is organized and functions largely stem from structural studies. Crystal structures of archaeal exosomes bound to RNA and of the corresponding nine-subunit human exosome cor...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2008.10.004
更新日期:2008-12-01 00:00:00
abstract::The wide occurrence of sialic acids (Sia) in various chemical forms linked as monomers or polymers in an outstanding position in a multitude of complex carbohydrates of animals and microorganisms renders them as most versatile function modulators in cell biology and pathology. A survey is presented of recent advances ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2009.06.003
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abstract::A remarkable group of proteins challenge the notions that protein sequence determines a unique three-dimensional structure, and that membrane and soluble proteins are very distinct. The pore-forming toxins typically transform from soluble, monomeric proteins to oligomers that form transmembrane channels. Recent struct...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2006.03.008
更新日期:2006-04-01 00:00:00
abstract::Many proteins are composed of protein domains, functional units of common descent. Multidomain forms are common in all eukaryotes making up more than half of the proteome and the evolution of novel domain architecture has been accelerated in metazoans. It is also becoming increasingly clear that alternative splicing i...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2013.02.013
更新日期:2013-06-01 00:00:00
abstract::Recently, advances have been made in methods and applications that integrate electron microscopy density maps and comparative modeling to produce atomic structures of macromolecular assemblies. Electron microscopy can benefit from comparative modeling through the fitting of comparative models into electron microscopy ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2005.08.001
更新日期:2005-10-01 00:00:00
abstract::Protein-protein interactions involving the catalytic domain of protein kinases are likely to be generally important in the regulation of signal transduction pathways, but are rather sparsely represented in crystal structures. Recently determined structures of the kinase domains of the mitogen-activated protein kinase ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2006.10.007
更新日期:2006-12-01 00:00:00
abstract::Due to the contribution of drug-target binding kinetics to drug efficacy, there is a high level of interest in developing methods to predict drug-target binding kinetic parameters. During the review period, a wide range of enhanced sampling molecular dynamics simulation-based methods has been developed for computing d...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2020.06.022
更新日期:2020-10-01 00:00:00
abstract::Cyanobacteriochrome photoreceptors are linear tetrapyrrole-binding photoreceptors that are distantly related to the canonical phytochrome photoreceptors. The chromophore-binding region of the cyanobacteriochromes consists of only a cGMP-phosphodiesterase/adenylate cyclase/FhlA (GAF) domain, while that of the phytochro...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2019.01.018
更新日期:2019-08-01 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
abstract::The radical intermediates generated during the catalytic cycles of adenosylcobalamin-dependent enzymes occur in pairs. The positions of radicals residing on the cofactor, substrate or protein, relative to the position of the low-spin Co(2+) from the cob(II)alamin intermediate, can be extracted from electron paramagnet...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/j.sbi.2003.10.011
更新日期:2003-12-01 00:00:00
abstract::Protein design efforts are beginning to yield molecules with many of the properties of natural proteins. Such experiments are informed by and contribute to our understanding of the sequence determinants of protein folding and stability. The most important design elements seem to be the proper placement of hydrophobic ...
journal_title:Current opinion in structural biology
pub_type: 杂志文章,评审
doi:10.1016/s0959-440x(96)80088-1
更新日期:1996-02-01 00:00:00