Abstract：
:Intrinsically disordered regions (IDRs) are fundamental units of protein function and regulation. Despite their inability to form a unique stable tertiary structure in isolation, many IDRs adopt a defined conformation upon binding and achieve their function through their interactions with other biomolecules. However, this requirement for IDR functionality seems to be at odds with the high entropic cost they must incur upon binding an interaction partner. How is this seeming paradox resolved? While increasing the enthalpy of binding is one approach to compensate for this entropic cost, growing evidence suggests that inherent features of IDRs, for instance repeating linear motifs, minimise the entropic cost of binding. Moreover, this control of entropic cost can be carefully modulated by a range of regulatory mechanisms, such as alternative splicing and post-translational modifications, which enable allosteric communication and rheostat-like tuning of IDR function. In that sense, the high entropic cost of IDR binding can be advantageous by providing tunability to protein function. In addition to biological regulatory mechanisms, modulation of entropy can also be controlled by environmental factors, such as changes in temperature, redox-potential and pH. These principles are extensively exploited by a number of organisms, including pathogens. They can also be utilised in bioengineering, synthetic biology and in pharmaceutical applications such as increasing bioavailability of protein therapeutics.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Flock T,Weatheritt RJ,Latysheva NS,Babu MMdoi
10.1016/j.sbi.2014.05.007subject
Has Abstractpub_date
2014-06-01 00:00:00pages
62-72eissn
0959-440Xissn
1879-033Xpii
S0959-440X(14)00061-Xjournal_volume
26pub_type
杂志文章,评审abstract：:Computational methods play an important role at all stages of the process of determining protein-protein interactions. They are used to predict potential interactions, to validate the results of high-throughput interaction screens and to analyze the protein networks inferred from interaction databases. ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(03)00070-8
更新日期：2003-06-01 00:00:00
abstract：:Covalent modifications of histone proteins regulate a wide variety of cellular processes. Methylation of histone H3K79 and H3K4 is associated with active transcription and is catalyzed by Dot1L and Set1, respectively. Both Dot1L and Set1 are activated by prior ubiquitination of histone H2B on K120 in a process termed ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.05.009
更新日期：2019-12-01 00:00:00
abstract：:The past two years have seen the extension of our knowledge on the cellular prion protein structure with new NMR data on both the hamster and human proteins. In addition, the folding dynamics of two cellular prion proteins have been elucidated. There are now several examples of recombinant prion proteins that are able...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(99)00051-2
更新日期：2000-02-01 00:00:00
abstract：:Newly synthesized proteins leave the ribosome through a narrow tunnel in the large subunit. During ongoing synthesis, nascent protein chains are particularly sensitive to aggregation and degradation because they emerge from the ribosome in an unfolded state. In bacteria, the first protein to interact with nascent chai...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2005.03.005
更新日期：2005-04-01 00:00:00
abstract：:Neutron diffraction provides different information from X-ray diffraction, because neutrons are scattered by atomic nuclei, whereas X-rays are scattered by electrons. One of the key advantages of neutron crystallography is the ability to visualize hydrogen and deuterium atoms, making it possible to observe the protona...
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
abstract：:2D-IR spectroscopy has matured to a powerful technique to study the structure and dynamics of peptides, but its extension to larger proteins is still in its infancy, the major limitations being sensitivity and selectivity. Site-selective information requires measuring single vibrational probes at sub-millimolar concen...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2015.03.012
更新日期：2015-10-01 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：:Molecular dynamics simulation studies of protein-nucleic acid complexes are more complicated than studies of either component alone-the force field has to be properly balanced, the systems tend to become very large, and a careful treatment of solvent and of electrostatic interactions is necessary. Recent investigation...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2007.12.012
更新日期：2008-04-01 00:00:00
abstract：:The amide bond with its planarity and lack of chemical reactivity is at the heart of protein structure. Chemical methylation of amides is known but was considered too harsh to be accessible to biology. Until last year there was no protein structure in the data bank with an enzymatically methylated amide. The discovery...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.06.004
更新日期：2020-12-01 00:00:00
abstract：:Generally, non-catalytic carbohydrate binding module (CBM) specificity has been shown to parallel the catalytic activity of the carbohydrate active enzyme (CAZyme) module it is appended to. With the rapid expansion in metagenomic sequence space for the potential discovery of new CBMs in addition to the recent emergenc...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.07.004
更新日期：2014-10-01 00:00:00
abstract：:Intermediate filaments are built from one to several members of a multigene family encoding fibrous proteins that share a highly conserved hierarchic assembly plan for the formation of multistranded filaments from distinctly structured extended coiled coils. Despite the rather low primary sequence identity, intermedia...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(98)80035-3
更新日期：1998-04-01 00:00:00
abstract：:The anaphase-promoting complex/cyclosome (APC/C) is a large multi-subunit complex that functions as a RING domain E3 ubiquitin ligase to regulate transitions through the cell cycle, achieved by controlling the defined ubiquitin-dependent degradation of specific cell cycle regulators. APC/C activity and substrate selec...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.11.010
更新日期：2020-04-01 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：:Membranes are sites of intense signaling activity within the cell, serving as dynamic scaffolds for the recruitment of signaling molecules and their substrates. The specific and reversible localization of these signaling molecules to membranes is critical for the appropriate activation of downstream signaling pathways...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.07.006
更新日期：2011-12-01 00:00:00
abstract：:The polyadenosine (poly(A)) tail found on the 3'-end of almost all eukaryotic mRNAs is important for mRNA stability and regulation of translation. mRNA 3'-end processing occurs co-transcriptionally and involves more than 20 proteins to specifically recognize the polyadenylation site, cleave the pre-mRNA, add a poly(A)...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.08.001
更新日期：2019-12-01 00:00:00
abstract：:The past year has seen some major advances in the area of carbohydrate synthesis using chemical methods. Progress in all areas of synthetic methodology, including new protecting groups and coupling methods, has been reported. A number of complex carbohydrate structures have been prepared using known, as well as new, m...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(00)00252-9
更新日期：2001-10-01 00:00:00
abstract：:Intrinsically disordered proteins (IDPs) are increasingly realized to play diverse biological roles, ranging from molecular signaling to the formation of membraneless organelles. Their high degree of disorder makes them more challenging to study using the techniques of conventional structural biology, because any obse...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2017.01.006
更新日期：2017-02-01 00:00:00
abstract：:Heparan sulfate (HS) is an essential and dynamic regulator of fibroblast growth factor (FGF) signaling. Two fundamentally different crystallographic models have been proposed to explain, at the molecular level, how HS/heparin enables FGF and FGF receptor (FGFR) to assemble into a functional dimer on the cell surface. ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2005.09.002
更新日期：2005-10-01 00:00:00
abstract：:Specific interactions between proteins and their molecular partners drive most biological processes, so understanding how these interactions evolve is an important question for biochemists and evolutionary biologists alike. It is often thought that ancestral proteins were systematically more promiscuous than modern pr...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2017.07.003
更新日期：2017-12-01 00:00:00
abstract：:Here we review mechanisms of protein evolution leading to structural changes in protein complexes. These mechanisms include mutations directly within protein interfaces, as well as the effects of mutations that propagate from distant regions of the protein. We also discuss the constraints protein complex structures im...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.07.004
更新日期：2013-12-01 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
更新日期：2011-10-01 00:00:00
abstract：:ATP-binding cassette (ABC) transporters are central to many physiological processes, including the uptake of nutrients, the non-classical secretion of signaling molecules and toxins, multidrug resistance and the development of human disease. As one might expect from this spectrum of translocation events, these ubiquit...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(02)00399-8
更新日期：2002-12-01 00:00:00
abstract：:Peptide-mediated interactions are gaining increased attention due to their predominant roles in the many regulatory processes that involve dynamic interactions between proteins. The structures of such interactions provide an excellent starting point for their characterization and manipulation, and can provide leads fo...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.07.006
更新日期：2013-12-01 00:00:00
abstract：:H+ transporting, reversible F-type ATPases (ATP synthases) and V-type ATPases share major structural features and function by similar mechanisms. Recent structural and genetic experiments provide new insights into the organization of the transmembrane and coupling sectors of the enzymes and the molecular mechanics of ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(96)80114-x
更新日期：1996-08-01 00:00:00
abstract：:Recent developments in experimental and computational aspects of NMR spectroscopy have had a significant impact on the accuracy and speed of macromolecular structure determination in solution, particularly with regard to systems of high complexity (such as protein complexes). These include experiments designed to prov...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(02)00302-0
更新日期：2002-04-01 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：:If protein structure prediction methods are to make any impact on the impending onerous task of analyzing the large numbers of unknown protein sequences generated by the ongoing genome-sequencing projects, it is vital that they make the difficult transition from computational 'gedankenexperiments' to practical softwar...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80055-3
更新日期：1997-06-01 00:00:00
abstract：:The past year has witnessed a tremendous increase in our understanding of the structures and interactions of the GTPases. The highlights include crystal structures of G alpha subunits, as well as the first complex between a GTPase (Rap1A) and an effector molecule (c-Raf1 Ras-binding domain). In the field of elongation...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80015-8
更新日期：1995-12-01 00:00:00
abstract：:The application of biocatalysis for the synthesis of glycans and glycoconjugates is a well-established and successful strategy, both for small and large scale synthesis. Compared to chemical synthesis, is has the advantage of high selectivity, but biocatalysis had been largely limited to natural glycans both in terms ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.07.004
更新日期：2020-12-01 00:00:00
abstract：:ATP-binding cassette (ABC)-type ATPases are chemo-mechanical engines for diverse biological pathways. ABC ATPase domains act not only in ABC transporters but also in DNA mismatch, nucleotide excision and double-strand break repair enzymes, as well as in chromosome segregation. Atomic-resolution crystal structures sugg...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(03)00037-x
更新日期：2003-04-01 00:00:00
