scholarly journals Unconventional conservation reveals structure-function relationships in the synaptonemal complex

eLife ◽  
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.

scholarly journals Unconventional conservation reveals structure-function relationships in the synaptonemal complex

2021 ◽  
Author(s):  
Lisa E Kursel ◽  
Henry D Cope ◽  
Ofer Rog
Keyword(s):  
Synaptonemal Complex ◽  
Protein Evolution ◽  
Coiled Coil ◽  
Structural Features ◽  
Coiled Coils ◽  
Functional Requirements ◽  
Universal Feature ◽  
Relative Arrangement ◽  
Primary Amino ◽  
And Function

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.

scholarly journals The Schizosaccharomyces pombe cho1+ Gene Encodes a Phospholipid Methyltransferase

Genetics ◽  
1998 ◽  
Vol 150 (2) ◽  
pp. 553-562
Author(s):  
Margaret I Kanipes ◽  
John E Hill ◽  
Susan A Henry
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Sequence Analysis ◽  
Schizosaccharomyces Pombe ◽  
Gene Disruption ◽  
Structure And Function ◽  
Biosynthetic Enzyme ◽  
Gene Encoding ◽  
Complementation Groups ◽  
Eukaryotic Organisms ◽  
And Function

Abstract The isolation of mutants of Schizosaccharomyces pombe defective in the synthesis of phosphatidylcholine via the methylation of phosphatidylethanolamine is reported. These mutants are choline auxotrophs and fall into two unlinked complementation groups, cho1 and cho2. We also report the analysis of the cho1+ gene, the first structural gene encoding a phospholipid biosynthetic enzyme from S. pombe to be cloned and characterized. The cho1+ gene disruption mutant (cho1Δ) is viable if choline is supplied and resembles the cho1 mutants isolated after mutagenesis. Sequence analysis of the cho1+ gene indicates that it encodes a protein closely related to phospholipid methyltransferases from Saccharomyces cerevisiae and rat. Phospholipid methyltransferases encoded by a rat liver cDNA and the S. cerevisiae OPI3 gene are both able to complement the choline auxotrophy of the S. pombe cho1 mutants. These results suggest that both the structure and function of the phospholipid N-methyltransferases are broadly conserved among eukaryotic organisms.

scholarly journals Cysteine-Free Proteins in the Immunobiology of Arthropod-Borne Diseases

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
J. Santiago Mejia ◽  
Erik N. Arthun ◽  
Richard G. Titus
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Distribution Patterns ◽  
Structural Features ◽  
Structure And Function ◽  
Cysteine Residues ◽  
Distribution Analysis ◽  
And Function ◽  
Abundance And Distribution ◽  
Host Parasite

One approach to identify epitopes that could be used in the design of vaccines to control several arthropod-borne diseases simultaneously is to look for common structural features in the secretome of the pathogens that cause them. Using a novel bioinformatics technique, cysteine-abundance and distribution analysis, we found that many different proteins secreted by several arthropod-borne pathogens, includingPlasmodium falciparum, Borrelia burgdorferi, and eight species of Proteobacteria, are devoid of cysteine residues. The identification of three cysteine-abundance and distribution patterns in several families of proteins secreted by pathogenic and nonpathogenic Proteobacteria, and not found when the amino acid analyzed was tryptophan, provides evidence of forces restricting the content of cysteine residues in microbial proteins during evolution. We discuss these findings in the context of protein structure and function, antigenicity and immunogenicity, and host-parasite relationships.

scholarly journals Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin

2002 ◽  
Vol 159 (6) ◽  
pp. 993-1004 ◽  
Author(s):  
Christine L. Humphries ◽  
Heath I. Balcer ◽  
Jessica L. D'Agostino ◽  
Barbara Winsor ◽  
David G. Drubin ◽  
...  
Keyword(s):  
Binding Protein ◽  
Coiled Coil ◽  
Actin Binding ◽  
Complex Activity ◽  
Actin Binding Protein ◽  
Coiled Coil Domain ◽  
Allele Specific ◽  
And Function

Mechanisms for activating the actin-related protein 2/3 (Arp2/3) complex have been the focus of many recent studies. Here, we identify a novel mode of Arp2/3 complex regulation mediated by the highly conserved actin binding protein coronin. Yeast coronin (Crn1) physically associates with the Arp2/3 complex and inhibits WA- and Abp1-activated actin nucleation in vitro. The inhibition occurs specifically in the absence of preformed actin filaments, suggesting that Crn1 may restrict Arp2/3 complex activity to the sides of filaments. The inhibitory activity of Crn1 resides in its coiled coil domain. Localization of Crn1 to actin patches in vivo and association of Crn1 with the Arp2/3 complex also require its coiled coil domain. Genetic studies provide in vivo evidence for these interactions and activities. Overexpression of CRN1 causes growth arrest and redistribution of Arp2 and Crn1p into aberrant actin loops. These defects are suppressed by deletion of the Crn1 coiled coil domain and by arc35-26, an allele of the p35 subunit of the Arp2/3 complex. Further in vivo evidence that coronin regulates the Arp2/3 complex comes from the observation that crn1 and arp2 mutants display an allele-specific synthetic interaction. This work identifies a new form of regulation of the Arp2/3 complex and an important cellular function for coronin.

scholarly journals In silico prediction of structure and function for a large family of transmembrane proteins that includes human Tmem41b

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1395
Author(s):  
Shahram Mesdaghi ◽  
David L. Murphy ◽  
Filomeno Sánchez Rodríguez ◽  
J. Javier Burgos-Mármol ◽  
Daniel J. Rigden
Keyword(s):  
Ab Initio ◽  
Rotational Symmetry ◽  
Domain Boundary ◽  
Pfam Domain ◽  
Transmembrane Proteins ◽  
Large Family ◽  
Data Bank ◽  
Structural Features ◽  
Structure And Function ◽  
And Function

Background: Recent strides in computational structural biology have opened up an opportunity to understand previously uncharacterised proteins.  The under-representation of transmembrane proteins in the Protein Data Bank highlights the need to apply new and advanced bioinformatics methods to shed light on their structure and function.  This study focuses on a family of transmembrane proteins containing the Pfam domain PF09335 ('SNARE_ASSOC'/ ‘VTT ‘/’Tvp38’). One prominent member, Tmem41b, has been shown to be involved in early stages of autophagosome formation and is vital in mouse embryonic development as well as being identified as a viral host factor of SARS-CoV-2. Methods: We used evolutionary covariance-derived information to construct and validate ab initio models, make domain boundary predictions and infer local structural features.  Results: The results from the structural bioinformatics analysis of Tmem41b and its homologues showed that they contain a tandem repeat that is clearly visible in evolutionary covariance data but much less so by sequence analysis.  Furthermore, cross-referencing of other prediction data with covariance analysis showed that the internal repeat features two-fold rotational symmetry.  Ab initio modelling of Tmem41b and homologues reinforces these structural predictions.  Local structural features predicted to be present in Tmem41b were also present in Cl-/H+ antiporters.  Conclusions: The results of this study strongly point to Tmem41b and its homologues being transporters for an as-yet uncharacterised substrate and possibly using H+ antiporter activity as its mechanism for transport.

scholarly journals Structural Features of a Bacteroidetes-Affiliated Cellulase Linked with a Polysaccharide Utilization Locus

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
A.E. Naas ◽  
A.K. MacKenzie ◽  
B. Dalhus ◽  
V.G.H. Eijsink ◽  
P.B. Pope
Keyword(s):  
Active Site ◽  
Three Dimensional ◽  
Structural Features ◽  
Structure And Function ◽  
Dimensional Structure ◽  
Active Site Cleft ◽  
Polysaccharide Utilization Locus ◽  
And Function ◽  
Rumen Metagenome

Abstract Previous gene-centric analysis of a cow rumen metagenome revealed the first potentially cellulolytic polysaccharide utilization locus, of which the main catalytic enzyme (AC2aCel5A) was identified as a glycoside hydrolase (GH) family 5 endo-cellulase. Here we present the 1.8 Å three-dimensional structure of AC2aCel5A and characterization of its enzymatic activities. The enzyme possesses the archetypical (β/α)8-barrel found throughout the GH5 family and contains the two strictly conserved catalytic glutamates located at the C-terminal ends of β-strands 4 and 7. The enzyme is active on insoluble cellulose and acts exclusively on linear β-(1,4)-linked glucans. Co-crystallization of a catalytically inactive mutant with substrate yielded a 2.4 Å structure showing cellotriose bound in the −3 to −1 subsites. Additional electron density was observed between Trp178 and Trp254, two residues that form a hydrophobic “clamp”, potentially interacting with sugars at the +1 and +2 subsites. The enzyme’s active-site cleft was narrower compared to the closest structural relatives, which in contrast to AC2aCel5A, are also active on xylans, mannans and/or xyloglucans. Interestingly, the structure and function of this enzyme seem adapted to less-substituted substrates such as cellulose, presumably due to the insufficient space to accommodate the side-chains of branched glucans in the active-site cleft.

scholarly journals IX. On the structure and development of the liver

1849 ◽  
Vol 139 ◽  
pp. 109-137 ◽  
Keyword(s):  
Royal Society ◽  
A Priori ◽  
Structural Features ◽  
Structure And Function ◽  
Conclusive Evidence ◽  
Interesting Paper ◽  
Biliary Ducts ◽  
And Function ◽  
Do So

In venturing to offer a second communication to the Royal Society respecting the structure of the liver, I feel the rather anxious to do so, that I may have an opportunity of correcting an error and supplying a deficiency which existed in my previous paper. In the following observations I purpose to present some account of the structure of the liver examined in the ascending series of animals, and also to describe the several stages of its evolution in the embryo; in this way I trust I may be able to exhibit the characteristic structural features of the organ as it exists in Man and the higher animals, and also to determine the true place which ought to be assigned to it in a classification of the various glandular organs occurring in the same. I am not aware that any detailed account of the structure of the liver has been recently published, except that by M. Natalis Guillot, which however, so far as I comprehend it, does not seem to be one that can be readily accepted; the idea that the minute biliary ducts and lymphatics originate together in a common net-work, is à priori improbable, and entirely opposed to conclusive evidence (as I think), which will be subsequently adduced. A very interesting paper on the structure and function of the liver has also appeared in the 4th volume of the Guy’s Hospital Reports, from the pen of Dr. Williams; to his labours I shall several times have occasion to refer, but it will be seen that I differ from him in several particulars, especially respecting the importance of the basement or limitary membrane.

Multimerization and tubulin binding are required for the SPIRAL2 protein to localize to and stabilize microtubule minus ends

2021 ◽  
Author(s):  
YUANWEI FAN ◽  
Natasha Bilkey ◽  
Ram Dixit
Keyword(s):  
Coiled Coil ◽  
Spatial Arrangement ◽  
In Planta ◽  
Structural Determinants ◽  
Coiled Coil Domain ◽  
Tubulin Binding ◽  
And Function ◽  
Necessary And Sufficient ◽  
Basic Region

Accruing evidence points to the control of microtubule minus-end dynamics as being crucial for the spatial arrangement and function of the microtubule cytoskeleton. In plants, the SPIRAL2 (SPR2) protein has emerged as a microtubule minus-end regulator that is structurally distinct from the animal minus-end regulators. Previously, SPR2 was shown to autonomously localize to microtubule minus ends and decrease their depolymerization rate. Here, we used in vitro and in planta experiments to identify the structural determinants required for SPR2 to recognize and stabilize microtubule minus ends. We show that SPR2 contains a single N-terminal TOG domain that binds to soluble tubulin. The TOG domain, a basic region, and coiled-coil domain are necessary and sufficient to target and stabilize microtubule minus ends. We demonstrate that the coiled-coil domain mediates multimerization of SPR2 that provides avidity for microtubule binding and is essential for binding to soluble tubulin. While TOG domain-containing proteins are traditionally thought to function as microtubule plus-end regulators, our results reveal that nature has repurposed the TOG domain of SPR2 to regulate microtubule minus ends.

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.

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