scholarly journals ARCIMBOLDOon coiled coils

2018 ◽  
Vol 74 (3) ◽  
pp. 194-204 ◽  
Author(s):  
Iracema Caballero ◽  
Massimo Sammito ◽  
Claudia Millán ◽  
Andrey Lebedev ◽  
Nicolas Soler ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Coiled Coils ◽  
Translational Symmetry ◽  
Command Line ◽  
Phase Problem ◽  
Final Solution ◽  
Resolution Limit ◽  
Helical Structures ◽  
Small Model ◽  
Test Pool

ARCIMBOLDOsolves the phase problem by combining the location of small model fragments usingPhaserwith density modification and autotracing usingSHELXE. Mainly helical structures constitute favourable cases, which can be solved using polyalanine helical fragments as search models. Nevertheless, the solution of coiled-coil structures is often complicated by their anisotropic diffraction and apparent translational noncrystallographic symmetry. Long, straight helices have internal translational symmetry and their alignment in preferential directions gives rise to systematic overlap of Patterson vectors. This situation has to be differentiated from the translational symmetry relating different monomers.ARCIMBOLDO_LITEhas been run on single workstations on a test pool of 150 coiled-coil structures with 15–635 amino acids per asymmetric unit and with diffraction data resolutions of between 0.9 and 3.0 Å. The results have been used to identify and address specific issues when solving this class of structures usingARCIMBOLDO. Features fromPhaserv.2.7 onwards are essential to correct anisotropy and produce translation solutions that will pass the packing filters. As the resolution becomes worse than 2.3 Å, the helix direction may be reversed in the placed fragments. Differentiation between true solutions and pseudo-solutions, in which helix fragments were correctly positioned but in a reverse orientation, was found to be problematic at resolutions worse than 2.3 Å. Therefore, after every new fragment-placement round, complete or sparse combinations of helices in alternative directions are generated and evaluated. The final solution is once again probed by helix reversal, refinement and extension. To conclude, density modification andSHELXEautotracing incorporating helical constraints is also exploited to extend the resolution limit in the case of coiled coils and to enhance the identification of correct solutions. This study resulted in a specialized mode withinARCIMBOLDOfor the solution of coiled-coil structures, which overrides the resolution limit and can be invoked from the command line (keyword coiled_coil) orARCIMBOLDO_LITEtask interface inCCP4i.

scholarly journals Distribution of disease-causing germline mutations in coiled-coils suggests essential role of their N-terminal region

2020 ◽  
Author(s):  
Zsofia E. Kalman ◽  
Bálint Mészáros ◽  
Zoltán Gáspári ◽  
Laszlo Dobson
Keyword(s):  
Essential Role ◽  
Coiled Coil ◽  
Germline Mutations ◽  
Coiled Coils ◽  
Helical Structures ◽  
Diverse Range ◽  
Human Proteins ◽  
Range Of Functions ◽  
Functional Explanations

AbstractNext-generation sequencing resulted in the identification of a huge number of naturally occurring variations in human proteins. The correct interpretation of the functional effects of these variations necessitates the understanding of how they modulate protein structure. Coiled-coils are α-helical structures responsible for a diverse range of functions, but most importantly, they facilitate the structural organization of macromolecular scaffolds via oligomerization. In this study, we analyzed a comprehensive set of disease-associated germline mutations in coiled-coil structures. Our results highlight the essential role of residues near the N-terminal part of coiled-coil regions, possibly critical for superhelix assembly and folding in some cases. We also show that coiled-coils of different oligomerization states exhibit characteristically distinct patterns of disease-causing mutations. Our study provides structural and functional explanations on how disease emerges through the mutation of these structural motifs.

scholarly journals Distribution of disease-causing germline mutations in coiled-coils implies an important role of their N-terminal region

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zsofia E. Kalman ◽  
Bálint Mészáros ◽  
Zoltán Gáspári ◽  
Laszlo Dobson
Keyword(s):  
Coiled Coil ◽  
Germline Mutations ◽  
Coiled Coils ◽  
Helical Structures ◽  
Diverse Range ◽  
Naturally Occurring ◽  
Human Proteins ◽  
Range Of Functions ◽  
Functional Explanations

Abstract Next-generation sequencing resulted in the identification of a huge number of naturally occurring variations in human proteins. The correct interpretation of the functional effects of these variations necessitates the understanding of how they modulate protein structure. Coiled-coils are α-helical structures responsible for a diverse range of functions, but most importantly, they facilitate the structural organization of macromolecular scaffolds via oligomerization. In this study, we analyzed a comprehensive set of disease-associated germline mutations in coiled-coil structures. Our results suggest an important role of residues near the N-terminal part of coiled-coil regions, possibly critical for superhelix assembly and folding in some cases. We also show that coiled-coils of different oligomerization states exhibit characteristically distinct patterns of disease-causing mutations. Our study provides structural and functional explanations on how disease emerges through the mutation of these structural motifs.

scholarly journals Extending the scope of coiled-coil crystal structure solution by AMPLE through improved ab initio modelling

2020 ◽  
Vol 76 (3) ◽  
pp. 272-284 ◽  
Author(s):  
Jens M. H. Thomas ◽  
Ronan M. Keegan ◽  
Daniel J. Rigden ◽  
Owen R. Davies
Keyword(s):  
Ab Initio ◽  
Coiled Coil ◽  
Coiled Coils ◽  
Molecular Replacement ◽  
Helical Structures ◽  
Major Barrier ◽  
X Ray Crystallography ◽  
Structure Solution ◽  
Coil Structure ◽  
Experimental Phasing

The phase problem remains a major barrier to overcome in protein structure solution by X-ray crystallography. In recent years, new molecular-replacement approaches using ab initio models and ideal secondary-structure components have greatly contributed to the solution of novel structures in the absence of clear homologues in the PDB or experimental phasing information. This has been particularly successful for highly α-helical structures, and especially coiled-coils, in which the relatively rigid α-helices provide very useful molecular-replacement fragments. This has been seen within the program AMPLE, which uses clustered and truncated ensembles of numerous ab initio models in structure solution, and is already accomplished for α-helical and coiled-coil structures. Here, an expansion in the scope of coiled-coil structure solution by AMPLE is reported, which has been achieved through general improvements in the pipeline, the removal of tNCS correction in molecular replacement and two improved methods for ab initio modelling. Of the latter improvements, enforcing the modelling of elongated helices overcame the bias towards globular folds and provided a rapid method (equivalent to the time requirements of the existing modelling procedures in AMPLE) for enhanced solution. Further, the modelling of two-, three- and four-helical oligomeric coiled-coils, and the use of full/partial oligomers in molecular replacement, provided additional success in difficult and lower resolution cases. Together, these approaches have enabled the solution of a number of parallel/antiparallel dimeric, trimeric and tetrameric coiled-coils at resolutions as low as 3.3 Å, and have thus overcome previous limitations in AMPLE and provided a new functionality in coiled-coil structure solution at lower resolutions. These new approaches have been incorporated into a new release of AMPLE in which automated elongated monomer and oligomer modelling may be activated by selecting `coiled-coil' mode.

scholarly journals Coiled-coil networking shapes cell molecular machinery

2012 ◽  
Vol 23 (19) ◽  
pp. 3911-3922 ◽  
Author(s):  
Yongqiang Wang ◽  
Xinlei Zhang ◽  
Hong Zhang ◽  
Yi Lu ◽  
Haolong Huang ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Critical Role ◽  
Coiled Coil ◽  
Coiled Coils ◽  
Protein Protein Interactions ◽  
Full Spectrum ◽  
Kinetochore Assembly ◽  
Genome Wide ◽  
Molecular Machinery ◽  
Systematic Understanding

The highly abundant α-helical coiled-coil motif not only mediates crucial protein–protein interactions in the cell but is also an attractive scaffold in synthetic biology and material science and a potential target for disease intervention. Therefore a systematic understanding of the coiled-coil interactions (CCIs) at the organismal level would help unravel the full spectrum of the biological function of this interaction motif and facilitate its application in therapeutics. We report the first identified genome-wide CCI network in Saccharomyces cerevisiae, which consists of 3495 pair-wise interactions among 598 predicted coiled-coil regions. Computational analysis revealed that the CCI network is specifically and functionally organized and extensively involved in the organization of cell machinery. We further show that CCIs play a critical role in the assembly of the kinetochore, and disruption of the CCI network leads to defects in kinetochore assembly and cell division. The CCI network identified in this study is a valuable resource for systematic characterization of coiled coils in the shaping and regulation of a host of cellular machineries and provides a basis for the utilization of coiled coils as domain-based probes for network perturbation and pharmacological applications.

scholarly journals α/β coiled coils

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Marcus D Hartmann ◽  
Claudia T Mendler ◽  
Jens Bassler ◽  
Ioanna Karamichali ◽  
Oswin Ridderbusch ◽  
...  
Keyword(s):  
Repeat Unit ◽  
Coiled Coil ◽  
Coiled Coils ◽  
Heptad Repeat ◽  
Protein Fold ◽  
Local Formation ◽  
Unexpected Formation ◽  
New Type ◽  
Backbone Structure ◽  
Level Of Understanding

Coiled coils are the best-understood protein fold, as their backbone structure can uniquely be described by parametric equations. This level of understanding has allowed their manipulation in unprecedented detail. They do not seem a likely source of surprises, yet we describe here the unexpected formation of a new type of fiber by the simple insertion of two or six residues into the underlying heptad repeat of a parallel, trimeric coiled coil. These insertions strain the supercoil to the breaking point, causing the local formation of short β-strands, which move the path of the chain by 120° around the trimer axis. The result is an α/β coiled coil, which retains only one backbone hydrogen bond per repeat unit from the parent coiled coil. Our results show that a substantially novel backbone structure is possible within the allowed regions of the Ramachandran space with only minor mutations to a known fold.

scholarly journals Integration of Rotation and Piston Motions in Coiled-Coil Signal Transduction

2007 ◽  
Vol 189 (16) ◽  
pp. 6048-6056 ◽  
Author(s):  
Rong Gao ◽  
David G. Lynn
Keyword(s):  
Coiled Coil ◽  
Dynamic Environment ◽  
Coiled Coils ◽  
Signal Integration ◽  
Signaling Mechanisms ◽  
Protein Receptor ◽  
Single Protein ◽  
Environmental Responses ◽  
Multiple Signaling ◽  
Host Signals

ABSTRACT A coordinated response to a complex and dynamic environment requires an organism to simultaneously monitor and interpret multiple signaling cues. In bacteria and some eukaryotes, environmental responses depend on the histidine autokinases (HKs). For example, VirA, a large integral membrane HK from Agrobacterium tumefaciens, regulates the expression of virulence genes in response to signals from multiple molecular classes (phenol, pH, and sugar). The ability of this pathogen to perceive inputs from different known host signals within a single protein receptor provides an opportunity to understand the mechanisms of signal integration. Here we exploited the conserved domain organization of the HKs and engineered chimeric kinases to explore the signaling mechanisms of phenol sensing and pH/sugar integration. Our data implicate a piston-assisted rotation of coiled coils for integration of multiple inputs and regulation of critical responses during pathogenesis.

scholarly journals Coiled-Coils: The Molecular Zippers that Self-Assemble Protein Nanostructures

2020 ◽  
Vol 21 (10) ◽  
pp. 3584 ◽  
Author(s):  
Won Min Park
Keyword(s):  
Modular Design ◽  
Coiled Coil ◽  
Molecular Complexes ◽  
Building Blocks ◽  
Structural Features ◽  
Coiled Coils ◽  
Design Strategies ◽  
Protein Motifs ◽  
Self Assembling ◽  
Current Design

Coiled-coils, the bundles of intertwined helical protein motifs, have drawn much attention as versatile molecular toolkits. Because of programmable interaction specificity and affinity as well as well-established sequence-to-structure relationships, coiled-coils have been used as subunits that self-assemble various molecular complexes in a range of fields. In this review, I describe recent advances in the field of protein nanotechnology, with a focus on programming assembly of protein nanostructures using coiled-coil modules. Modular design approaches to converting the helical motifs into self-assembling building blocks are described, followed by a discussion on the molecular basis and principles underlying the modular designs. This review also provides a summary of recently developed nanostructures with a variety of structural features, which are in categories of unbounded nanostructures, discrete nanoparticles, and well-defined origami nanostructures. Challenges existing in current design strategies, as well as desired improvements for controls over material properties and functionalities for applications, are also provided.

Hierarchical nanomechanics of vimentin alpha helical coiled-coil proteins

2006 ◽  
Vol 978 ◽  
Author(s):  
Theodor Ackbarow ◽  
Markus J. Buehler
Keyword(s):  
Atomistic Simulation ◽  
Coiled Coil ◽  
Building Blocks ◽  
Tensile Tests ◽  
Coiled Coils ◽  
Atomistic Modeling ◽  
Alpha Helices ◽  
Hierarchical Assembly ◽  
Leading Role ◽  
Elementary Building

AbstractCoiled-coil alpha-helical dimers are the elementary building blocks of intermediate filaments (IFs), an important component of the cell's cytoskeleton. Therefore, IFs play a leading role in the mechanical integrity of the cells. Here we use atomistic simulation to carry out tensile tests on coiled-coils as well as on single alpha-helices of the 2B segment of the vimentin dimer that has been shown to control the large-deformation behavior of cells. We compare the characteristic force-strain curves of both structures and suggest explanations for the differences on this fundamental level of hierarchical assembly. We further systematically explore the strain rate dependence of the mechanical properties of the vimentin coiled-coil protein. We develop a simple continuum model capable of reproducing the atomistic modeling results. The model enables us to extrapolate to much lower deformation rates approaching those used in experiment.

scholarly journals Suppressor screening reveals common kleisin–hinge interaction in condensin and cohesin, but different modes of regulation

2019 ◽  
Vol 116 (22) ◽  
pp. 10889-10898 ◽  
Author(s):  
Xingya Xu ◽  
Mitsuhiro Yanagida
Keyword(s):  
Chromatin Remodeling ◽  
Chromosome Segregation ◽  
Coiled Coil ◽  
Coiled Coils ◽  
Whole Genome ◽  
Chromatid Cohesion ◽  
Suppression Mechanism ◽  
Elimination Pathway ◽  
Extragenic Suppressors ◽  
Structural Maintenance Of Chromosomes

Cohesin and condensin play fundamental roles in sister chromatid cohesion and chromosome segregation, respectively. Both consist of heterodimeric structural maintenance of chromosomes (SMC) subunits, which possess a head (containing ATPase) and a hinge, intervened by long coiled coils. Non-SMC subunits (Cnd1, Cnd2, and Cnd3 for condensin; Rad21, Psc3, and Mis4 for cohesin) bind to the SMC heads. Here, we report a large number of spontaneous extragenic suppressors for fission yeast condensin and cohesin mutants, and their sites were determined by whole-genome sequencing. Mutants of condensin’s non-SMC subunits were rescued by impairing the SUMOylation pathway. Indeed, SUMOylation of Cnd2, Cnd3, and Cut3 occurs in midmitosis, and Cnd3 K870 SUMOylation functionally opposes Cnd subunits. In contrast, cohesin mutants rad21 and psc3 were rescued by loss of the RNA elimination pathway (Erh1, Mmi1, and Red1), and loader mutant mis4 was rescued by loss of Hrp1-mediated chromatin remodeling. In addition, distinct regulations were discovered for condensin and cohesin hinge mutants. Mutations in the N-terminal helix bundle [containing a helix–turn–helix (HTH) motif] of kleisin subunits (Cnd2 and Rad21) rescue virtually identical hinge interface mutations in cohesin and condensin, respectively. These mutations may regulate kleisin’s interaction with the coiled coil at the SMC head, thereby revealing a common, but previously unknown, suppression mechanism between the hinge and the kleisin N domain, which is required for successful chromosome segregation. We propose that in both condensin and cohesin, the head (or kleisin) and hinge may interact and collaboratively regulate the resulting coiled coils to hold and release chromosomal DNAs.

Address of the President Sir Alan Hodgkin, O. M. at the Anniversary Meeting, 1 December 1975

1976 ◽  
Vol 192 (1109) ◽  
pp. 371-391
Keyword(s):  
Molecular Biology ◽  
Coiled Coil ◽  
Helical Structure ◽  
X Ray Diffraction ◽  
Helical Structures ◽  
X Ray ◽  
Double Helical Structure ◽  
Leading Role ◽  
Replication Scheme ◽  
Related Proteins

The Copley Medal is awarded to Dr F. H. C. Crick, F. R. S. In 1953 Crick and Watson proposed the double-helical model for DNA, in which the bases are arranged in complementary pairs so that the molecule is capable of self-replication and is thus the essential carrier of genetic information in living cells. This proposal was based on an inspired interpretation of the results of X-ray diffraction analysis of DNA carried out by Wilkins, Franklin and their collaborators, and on the chemical analyses of Chargaff and others. The replication scheme inherent in the double-helical structure of DNA made it possible for the first time to discuss the mechanism of heredity in molecular terms; it has been the most fruitful concept in the whole of biology during the past 25 years, and has been the basis for the explosive development of molecular biology. Besides his part in this dramatic discovery, Crick played a very important part in increasing our understanding of the way in which the genetic message is carried on DNA (the ‘coding’ problem), and of the mechanisms by which it is translated into specific sequences of amino acids in the proteins synthesized by the cell. He has also continued to play a leading rôle in many other aspects of molecular biology, and has made important contributions to X-ray studies of crystalline proteins, fibrous proteins and viruses. These include the theory of diffraction from helical structures, the coiled-coil model of α-keratin and related proteins, the structure of collagen, and the theoretical basis of the construction of ‘spherical’ viruses. More recently, Crick has had an important influence on work in the fields of development and of chromosome structure.

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