Unconventional conservation reveals structure-function relationships in the synaptonemal complex

Functional requirements constrain protein evolution, commonly manifesting in conserved primary amino acid sequence. Here, we extend this idea to secondary structural features by tracking their conservation in essential meiotic proteins with highly diverged sequences. The synaptonemal complex (SC) aligns parental chromosome pairs and regulates exchanges between them. In electron micrographs of meiocytes from all eukaryotic clades, the SC appears as a ~100 nm-wide ladder-like structure with regular striations. Despite the conserved ultrastructure and functions, the proteins that make up the SC are highly divergent in sequence. Here we found that, within the Caenorhabditis genus, SC proteins are significantly more diverged than other proteins. However, SC proteins have highly conserved protein length and coiled-coil domain structure. The same unconventional conservation signature holds true for SC proteins in Drosophila and mammals, suggesting it could be a universal feature of SC proteins. We used this evolutionary signature to identify a novel SC protein in the nematode Pristionchus pacificus, Ppa-SYP-1, which has no significant homology to any protein outside of Pristionchus. Our work suggests that the length and relative arrangement of coiled-coils play a key role in the structure and function of the SC. Furthermore, our analysis implies that expanding sequence analysis beyond measures of per-site identity or similarity can enhance our understanding of protein evolution and function.

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Unconventional conservation reveals structure-function relationships in the synaptonemal complex

eLife ◽

10.7554/elife.72061 ◽

2021 ◽

Vol 10 ◽

Author(s):

Lisa E Kursel ◽

Henry D Cope ◽

Ofer Rog

Keyword(s):

Sequence Analysis ◽

Synaptonemal Complex ◽

Protein Evolution ◽

Coiled Coil ◽

Structural Features ◽

Structure And Function ◽

Coiled Coils ◽

Functional Requirements ◽

Coiled Coil Domain ◽

And Function

Functional requirements constrain protein evolution, commonly manifesting in a conserved amino acid sequence. Here, we extend this idea to secondary structural features by tracking their conservation in essential meiotic proteins with highly diverged sequences. The synaptonemal complex (SC) is a ~100-nm-wide ladder-like meiotic structure present in all eukaryotic clades, where it aligns parental chromosomes and regulates exchanges between them. Despite the conserved ultrastructure and functions of the SC, SC proteins are highly divergent within Caenorhabditis. However, SC proteins have highly conserved length and coiled-coil domain structure. We found the same unconventional conservation signature in Drosophila and mammals, and used it to identify a novel SC protein in Pristionchus pacificus, Ppa-SYP-1. Our work suggests that coiled-coils play wide-ranging roles in the structure and function of the SC, and more broadly, that expanding sequence analysis beyond measures of per-site similarity can enhance our understanding of protein evolution and function.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21103584 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3584 ◽

Cited By ~ 1

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.

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DeepCoil—a fast and accurate prediction of coiled-coil domains in protein sequences

Bioinformatics ◽

10.1093/bioinformatics/bty1062 ◽

2019 ◽

Vol 35 (16) ◽

pp. 2790-2795 ◽

Cited By ~ 23

Author(s):

Jan Ludwiczak ◽

Aleksander Winski ◽

Krzysztof Szczepaniak ◽

Vikram Alva ◽

Stanislaw Dunin-Horkawicz

Keyword(s):

Coiled Coil ◽

Protein Sequences ◽

Coiled Coils ◽

Supplementary Information ◽

Biological Interactions ◽

Structural Domains ◽

Current State ◽

Genome Wide ◽

And Function ◽

Higher Sensitivity

Abstract Motivation Coiled coils are protein structural domains that mediate a plethora of biological interactions, and thus their reliable annotation is crucial for studies of protein structure and function. Results Here, we report DeepCoil, a new neural network-based tool for the detection of coiled-coil domains in protein sequences. In our benchmarks, DeepCoil significantly outperformed current state-of-the-art tools, such as PCOILS and Marcoil, both in the prediction of canonical and non-canonical coiled coils. Furthermore, in a scan of the human genome with DeepCoil, we detected many coiled-coil domains that remained undetected by other methods. This higher sensitivity of DeepCoil should make it a method of choice for accurate genome-wide detection of coiled-coil domains. Availability and implementation DeepCoil is written in Python and utilizes the Keras machine learning library. A web server is freely available at https://toolkit.tuebingen.mpg.de/#/tools/deepcoil and a standalone version can be downloaded at https://github.com/labstructbioinf/DeepCoil. Supplementary information Supplementary data are available at Bioinformatics online.

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Structure and function of Spc42 coiled-coils in yeast centrosome assembly and duplication

Molecular Biology of the Cell ◽

10.1091/mbc.e19-03-0167 ◽

2019 ◽

Vol 30 (12) ◽

pp. 1505-1522 ◽

Cited By ~ 1

Author(s):

Amanda C. Drennan ◽

Shivaani Krishna ◽

Mark A. Seeger ◽

Michael P. Andreas ◽

Jennifer M. Gardner ◽

...

Keyword(s):

Coiled Coil ◽

Core Layer ◽

Spindle Pole ◽

Coiled Coils ◽

Lipid Monolayer ◽

Functional Roles ◽

Spindle Pole Bodies ◽

And Function

Centrosomes and spindle pole bodies (SPBs) are membraneless organelles whose duplication and assembly is necessary for bipolar mitotic spindle formation. The structural organization and functional roles of major proteins in these organelles can provide critical insights into cell division control. Spc42, a phosphoregulated protein with an N-terminal dimeric coiled-coil (DCC), assembles into a hexameric array at the budding yeast SPB core, where it functions as a scaffold for SPB assembly. Here, we present in vitro and in vivo data to elucidate the structural arrangement and biological roles of Spc42 elements. Crystal structures reveal details of two additional coiled-coils in Spc42: a central trimeric coiled-coil and a C-terminal antiparallel DCC. Contributions of the three Spc42 coiled-coils and adjacent undetermined regions to the formation of an ∼145 Å hexameric lattice in an in vitro lipid monolayer assay and to SPB duplication and assembly in vivo reveal structural and functional redundancy in Spc42 assembly. We propose an updated model that incorporates the inherent symmetry of these Spc42 elements into a lattice, and thereby establishes the observed sixfold symmetry. The implications of this model for the organization of the central SPB core layer are discussed.

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A library of coiled-coil domains: from regular bundles to peculiar twists

Bioinformatics ◽

10.1093/bioinformatics/btaa1041 ◽

2020 ◽

Author(s):

Krzysztof Szczepaniak ◽

Adriana Bukala ◽

Antonio Marinho da Silva Neto ◽

Jan Ludwiczak ◽

Stanislaw Dunin-Horkawicz

Keyword(s):

Protein Data Bank ◽

Conformational Changes ◽

Coiled Coil ◽

Data Bank ◽

Structural Features ◽

Coiled Coils ◽

Supplementary Information ◽

Numerical Representation ◽

Data Set ◽

Potential Applications

Abstract Motivation Coiled coils are widespread protein domains involved in diverse processes ranging from providing structural rigidity to the transduction of conformational changes. They comprise two or more α-helices that are wound around each other to form a regular supercoiled bundle. Owing to this regularity, coiled-coil structures can be described with parametric equations, thus enabling the numerical representation of their properties, such as the degree and handedness of supercoiling, rotational state of the helices, and the offset between them. These descriptors are invaluable in understanding the function of coiled coils and designing new structures of this type. The existing tools for such calculations require manual preparation of input and are therefore not suitable for the high-throughput analyses. Results To address this problem, we developed SamCC-Turbo, a software for fully-automated, per-residue measurement of coiled coils. By surveying Protein Data Bank with SamCC-Turbo, we generated a comprehensive atlas of ∼50,000 coiled-coil regions. This machine learning-ready data set features precise measurements as well as decomposes coiled-coil structures into fragments characterized by various degrees of supercoiling. The potential applications of SamCC-Turbo are exemplified by analyses in which we reveal general structural features of coiled coils involved in functions requiring conformational plasticity. Finally, we discuss further directions in the prediction and modeling of coiled coils. Availability SamCC-Turbo is available as a web server (https://lbs.cent.uw.edu.pl/samcc_turbo) and as a Python library (https://github.com/labstructbioinf/samcc_turbo), whereas the results of the Protein Data Bank scan can be browsed and downloaded at https://lbs.cent.uw.edu.pl/ccdb. Supplementary information Supplementary data are available at Bioinformatics online.

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The Synaptonemal Complex Protein SCP3 Can Form Multistranded, Cross-striated Fibers In Vivo

The Journal of Cell Biology ◽

10.1083/jcb.142.2.331 ◽

1998 ◽

Vol 142 (2) ◽

pp. 331-339 ◽

Cited By ~ 68

Author(s):

Li Yuan ◽

Jeanette Pelttari ◽

Eva Brundell ◽

Birgitta Björkroth ◽

Jian Zhao ◽

...

Keyword(s):

Synaptonemal Complex ◽

Coiled Coil ◽

Specific Protein ◽

Lateral Element ◽

Transmission Electron ◽

Complex Protein ◽

Synaptonemal Complex Protein ◽

And Function ◽

20 Nm

The synaptonemal complex protein SCP3 is part of the lateral element of the synaptonemal complex, a meiosis-specific protein structure essential for synapsis of homologous chromosomes. We have investigated the fiber-forming properties of SCP3 to elucidate its role in the synaptonemal complex. By synthesis of SCP3 in cultured somatic cells, it has been shown that SCP3 can self-assemble into thick fibers and that this process requires the COOH-terminal coiled coil domain of SCP3, as well as the NH2-terminal nonhelical domain. We have further analyzed the thick SCP3 fibers by transmission electron microscopy and immunoelectron microscopy. We found that the fibers display a transversal striation with a periodicity of ∼20 nm and consist of a large number of closely associated, thin fibers, 5–10 nm in diameter. These features suggest that the SCP3 fibers are structurally related to intermediate filaments. It is known that in some species the lateral elements of the synaptonemal complex show a highly ordered striated structure resembling that of the SCP3 fibers. We propose that SCP3 fibers constitute the core of the lateral elements of the synaptonemal complex and function as a molecular framework to which other proteins attach, regulating DNA binding to the chromatid axis, sister chromatid cohesion, synapsis, and recombination.

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Design of two-stranded and three-stranded coiled-coil peptides

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1995.0048 ◽

1995 ◽

Vol 348 (1323) ◽

pp. 81-88 ◽

Cited By ~ 52

Keyword(s):

Protein Design ◽

De Novo ◽

Coiled Coil ◽

Structural Features ◽

Coiled Coils ◽

General Sequence ◽

The Third ◽

Cooperative Equilibrium ◽

High Concentrations ◽

Propensity Scale

The structural features required for the formation of two- versus three-stranded coiled coils have been explored using de novo protein design. Peptides with leucine at the ‘a’ and ‘d’ positions of a coiled-coil (general sequence: Leu a Xaa b Xaa c Leu d Glu e Xaa f Lys g ) exist in a non-cooperative equilibrium between unstructured monomers and helical dimers and helical trimers. Substituting valine into each ‘a’ position produces peptides which still form trimers at high concentrations, whereas substitution of a single asparagine at the ‘a’ position of the third heptad yields a dimer. During the course of this work, we also re-investigated a helical propensity scale derived using a series of coiled-coil peptides previously believed to exist in a monomer-dimer equilibrium (O’Neil & DeGrado 1990). Detailed analysis of the concentration dependence of ellipticity at 222 nm reveals that they exist in a non-cooperative monomer-dimer-trimer equilibrium. However, the concentration of trimer near the midpoint of the concentration-dependent transition is small, so the previously determined values of ΔΔG α using the approximate monomer-dimer scheme are indistinguishable from the values obtained employing the complete monomer-dimer-trimer equilibrium.

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Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Cells ◽

10.3390/cells10081960 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1960

Author(s):

K. Tanuj Sapra ◽

Ohad Medalia

Keyword(s):

Intermediate Filaments ◽

Eukaryotic Cell ◽

Coiled Coils ◽

Cellular Functions ◽

Mechanical Pressure ◽

Mechanical Feature ◽

Cellular Processes ◽

Nuclear Lamins ◽

Filament Networks ◽

And Function

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin.

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kangaroo, a Mobile Element From Volvox carteri, Is a Member of a Newly Recognized Third Class of Retrotransposons

Genetics ◽

10.1093/genetics/162.4.1617 ◽

2002 ◽

Vol 162 (4) ◽

pp. 1617-1630

Author(s):

Leonard Duncan ◽

Kristine Bouckaert ◽

Fay Yeh ◽

David L Kirk

Keyword(s):

Genomic Structure ◽

Mobile Element ◽

Direct Repeat ◽

Structural Features ◽

Volvox Carteri ◽

Developmentally Regulated ◽

Closed Circle ◽

Integration Mechanisms ◽

And Function

Abstract Retrotransposons play an important role in the evolution of genomic structure and function. Here we report on the characterization of a novel retrotransposon called kangaroo from the multicellular green alga, Volvox carteri. kangaroo elements are highly mobile and their expression is developmentally regulated. They probably integrate via double-stranded, closed-circle DNA intermediates through the action of an encoded recombinase related to the λ-site-specific integrase. Phylogenetic analysis indicates that kangaroo elements are closely related to other unorthodox retrotransposons including PAT (from a nematode), DIRS-1 (from Dictyostelium), and DrDIRS1 (from zebrafish). PAT and kangaroo both contain split direct repeat (SDR) termini, and here we show that DIRS-1 and DrDIRS1 elements contain terminal features structurally related to SDRs. Thus, these mobile elements appear to define a third class of retrotransposons (the DIRS1 group) that are unified by common structural features, genes, and integration mechanisms, all of which differ from those of LTR and conventional non-LTR retrotransposons.

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Myosinome: A Database of Myosins from Select Eukaryotic Genomes to Facilitate Analysis of Sequence-Structure-Function Relationships

Bioinformatics and Biology Insights ◽

10.4137/bbi.s9902 ◽

2012 ◽

Vol 6 ◽

pp. BBI.S9902 ◽

Cited By ~ 3

Author(s):

Divya P. Syamaladevi ◽

Margaret S Sunitha ◽

S. Kalaimathy ◽

Chandrashekar C. Reddy ◽

Mohammed Iftekhar ◽

...

Keyword(s):

Conformational Changes ◽

Atp Hydrolysis ◽

Homo Sapiens ◽

Relevant Literature ◽

Myosin Ii ◽

Coiled Coil ◽

Structural Features ◽

Model Organisms ◽

Congenital Diseases ◽

C Elegans

Myosins are one of the largest protein superfamilies with 24 classes. They have conserved structural features and catalytic domains yet show huge variation at different domains resulting in a variety of functions. Myosins are molecules driving various kinds of cellular processes and motility until the level of organisms. These are ATPases that utilize the chemical energy released by ATP hydrolysis to bring about conformational changes leading to a motor function. Myosins are important as they are involved in almost all cellular activities ranging from cell division to transcriptional regulation. They are crucial due to their involvement in many congenital diseases symptomatized by muscular malfunctions, cardiac diseases, deafness, neural and immunological dysfunction, and so on, many of which lead to death at an early age. We present Myosinome, a database of selected myosin classes (myosin II, V, and VI) from five model organisms. This knowledge base provides the sequences, phylogenetic clustering, domain architectures of myosins and molecular models, structural analyses, and relevant literature of their coiled-coil domains. In the current version of Myosinome, information about 71 myosin sequences belonging to three myosin classes (myosin II, V, and VI) in five model organisms ( Homo Sapiens, Mus musculus, D. melanogaster, C. elegans and S. cereviseae) identified using bioinformatics surveys are presented, and several of them are yet to be functionally characterized. As these proteins are involved in congenital diseases, such a database would be useful in short-listing candidates for gene therapy and drug development. The database can be accessed from http://caps.ncbs.res.in/myosinome .

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