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 that mutational perturbations consistently modulate the packing and dynamics of a significant fraction of protein residues, even those that are located >10-15 Å from the mutated site. Such long-range modulation of protein features can distinctly tune protein stability and the native conformational ensemble contributing to allosteric modulation of function. In this review, I summarize a series of experimental and computational observations that highlight the incredibly pliable nature of proteins and their response to mutational perturbations manifested via the intra-protein interaction network. I highlight how an intimate understanding of mutational effects could pave the way for integrating stability, folding, cooperativity and even allostery within a single physical framework.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Naganathan ANdoi
10.1016/j.sbi.2018.09.004subject
Has Abstractpub_date
2019-02-01 00:00:00pages
1-9eissn
0959-440Xissn
1879-033Xpii
S0959-440X(18)30053-8journal_volume
54pub_type
杂志文章,评审abstract：:The first high-resolution structure of a P-type ATPase, that of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum, was published in 2000. This structure has provided many clues to how the Ca(2+)-ATPase might work, but no complete answers. The Ca(2+)-ATPase structure reveals no clear pathway from the cytoplas...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(02)00360-3
更新日期：2002-08-01 00:00:00
abstract：:While there have been impressive advances in understanding protein folding over the past few decades, we are still far from the goal of solving the protein folding problem: predicting the folding pathway and final structure entirely from the amino acid sequence. One reason for this shortcoming may be the lack of under...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2012.10.003
更新日期：2013-02-01 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：: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：: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
abstract：:The structure of the visual pigment rhodopsin in the dark state was first investigated by electron microscopy (EM). More recently, rhodopsin has been crystallised in two different space groups--a tetragonal P4(1) crystal form and a trigonal P3(1) packing arrangement. The structures of the pigment, determined by X-ray ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2005.07.010
更新日期：2005-08-01 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：:Molecular flexibility over a wide time range is of central importance to the function of many proteins, both soluble and membrane. Revealing the modes of flexibility, their amplitudes, and time scales under physiological conditions is the challenge for spectroscopic methods, one of which is site-directed spin labeling...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.06.008
更新日期：2013-10-01 00:00:00
abstract：:Recently, atomic models of the mammalian, fungal and the bacterial fatty acid synthases type I (FAS I) were reported. Now, a wealth of functional data, collected during the last decades, can be embedded into structural frames. But there is more, which remains to be done! Our current considerations are implicitly very ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.12.004
更新日期：2014-04-01 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：:There has been significant recent progress in the computational design of protein interactions including the creation of novel heterodimers, homodimers, nanohedra, fibril caps and a protein crystal. Essential to these successes has been the use of innovative strategies for finding binding modes that are achievable, th...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.04.010
更新日期：2013-08-01 00:00:00
abstract：:Solid-state NMR (ssNMR) offers insight into the formation of protein complexes and ligand binding for a large range of molecular sizes and binding affinities. Recent instrumental and methodological progress has enabled novel possibilities for using multi-dimensional ssNMR to study molecular 3D structures and interacti...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.08.003
更新日期：2006-10-01 00:00:00
abstract：:Transmembrane helix-helix interactions mediate the folding and assembly of membrane proteins. Recognition motifs range from GxxxG and leucine zippers to polar side chains and salt bridges. Some canonical membrane proteins contain local charge clusters that are important for folding and function, and which have to be c...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.05.003
更新日期：2014-08-01 00:00:00
abstract：:2-Oxoacid:ferredoxin oxidoreductases (OFORs) are essential enzymes in microbial one-carbon metabolism. They use thiamine pyrophosphate to reversibly cleave carbon-carbon bonds, generating low potential (∼-500mV) electrons. Crystallographic analysis of a recently discovered OFOR, an oxalate oxidoreductase (OOR), has pr...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.05.011
更新日期：2016-12-01 00:00:00
abstract：:Directed evolution is widely used to improve enzymes, particularly for industrial biocatalytic processes. Molecular biology advances present many new strategies for directed evolution. Commonly used techniques have led to many successful examples of enzyme improvement, yet there is still a need to improve both the eff...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.05.003
更新日期：2011-08-01 00:00:00
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, ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.05.007
更新日期：2014-06-01 00:00:00
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
更新日期：2005-02-01 00:00:00
abstract：:Ring-shaped nucleic acid translocases and helicases catalyze the directed and processive movement of nucleic acid strands to support essential transactions such as replication, transcription, and chromosome partitioning. Assembled typically as hexamers, ring helicase/translocase systems use coordinated cycles of nucle...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.11.006
更新日期：2014-04-01 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：:The molecular bases of thermal and cold stability and adaptation, which allow proteins to remain folded and functional in the temperature ranges in which their host organisms live and grow, are still only partially elucidated. Indeed, both experimental and computational studies fail to yield a fully precise and global...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.12.007
更新日期：2017-02-01 00:00:00
abstract：:Ising-like models have been remarkably successful in reproducing all the experimental data available on the equilibrium and kinetics of secondary structure formation in short peptides. Over the past two years, very similar models have been used to predict the folding of complete proteins, with encouraging results. Alt...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(00)00192-5
更新日期：2001-04-01 00:00:00
abstract：:Proteins are chief actors in life that perform a myriad of exquisite functions. This diversity has been enabled through the evolution and diversification of protein folds. Analysis of sequences and structures strongly suggest that numerous protein pieces have been reused as building blocks and propagated to many moder...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.12.007
更新日期：2021-01-13 00:00:00
abstract：:The modulation of enzyme function is a key regulatory feature of biological systems. The ability to engineer synthetic enzymes that can be controlled by any arbitrary signal would enable a wide array of sensing applications and therapeutics and provide us with powerful tools for the basic study of biology. Here severa...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2009.04.007
更新日期：2009-08-01 00:00:00
abstract：:C-type lectins are the largest and most diverse family of mammalian carbohydrate-binding proteins. They share a common protein fold, which provides the unifying basis for calcium-mediated carbohydrate recognition. Their involvement in a multitude of biological functions is remarkable. Here, we review the variety of ta...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.11.003
更新日期：2020-06-01 00:00:00
abstract：:Assembly line polyketide synthases (PKSs) are remarkable biosynthetic machines with considerable potential for structure-based engineering. Several types of protein-protein interactions, both within and between PKS modules, play important roles in the catalytic cycle of a multimodular PKS. Additionally, vectorial bios...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.05.009
更新日期：2016-12-01 00:00:00
abstract：:Current knowledge about the determinants of beta-sheet formation has been notably improved by the structural and kinetic analysis of model peptides, by mutagenesis experiments in proteins and by the statistical analysis of the protein structure database (Protein Data Bank; PDB). In the past year, several peptides comp...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(99)80069-4
更新日期：1999-08-01 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：: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：:Structures of two restriction endonucleases, BamHI and PvuII, were reported in the past year. This doubles the number of restriction endonuclease structures now known from two to four, and enables a comparative analysis of their structures and modes of DNA recognition. Despite a lack of sequence homology between the e...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80004-k
更新日期：1995-02-01 00:00:00
abstract：:Achieving the goals of structural genomics initiatives depends on the outcomes of two groups of factors: the number and distribution of experimentally determined protein structures, and our ability to assign novel proteins to known structures (fold recognition) and use them to build models (modeling). The quality of t...
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
