Martín Graña

Martín Graña
Institut Pasteur de Montevideo | IP Montevideo · bioinformatics

PhD, research associate

About

49
Publications
5,363
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Introduction
Martín Graña works at the Bioinformatics Unit from Institut Pasteur de Montevideo. His research uses concepts/methods from Bioinformatics, Evolutionary Biology and Structural Biology.

Publications

Publications (49)
Preprint
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Sexual reproduction in Eukarya consists of genome reduction by meiosis and subsequent gamete fusion. The presence of meiotic genes in Archaea and Bacteria suggests that prokaryotic DNA repair mechanisms evolved towards meiotic recombination 1, 2 . However, the evolutionary origin of gamete fusion is less clear because fusogenic proteins resembling...
Article
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Bacteria control the metabolic processes by which they obtain nutrients and energy in order to adapt to the environment. ActinobacteriaCorynebacterium glutamicum
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Human mitochondrial diseases are a group of heterogeneous diseases caused by defects in oxidative phosphorylation, due to mutations in mitochondrial (mtDNA) or nuclear DNA. The diagnosis of mitochondrial disease is challenging since mutations in multiple genes can affect mitochondrial function, there is considerable clinical variability and a poor...
Preprint
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Signal transduction is essential for bacteria to adapt to changing environmental conditions. Among many forms of post-translational modifications, reversible protein phosphorylation has evolved as a ubiquitous molecular mechanism of protein regulation in response to specific stimuli. The Ser/Thr protein kinase PknG modulates the fate of intracellul...
Article
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Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms. Notably, among the multiple factors that tether FtsZ to the membrane during bacterial cell constriction, archaea only possess SepF-like homologs. Here, we combine structu...
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Background Rare diseases are pathologies that affect less than 1 in 2000 people. They are difficult to diagnose due to their low frequency and their often highly heterogeneous symptoms. Rare diseases have in general a high impact on the quality of life and life expectancy of patients, which are in general children or young people. The advent of hig...
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Uruguay is one of the few countries in the Americas that successfully contained the coronavirus disease 19 (COVID-19) epidemic during the first half of 2020. Nevertheless, the intensive human mobility across the dry border with Brazil is a major challenge for public health authorities. We aimed to investigate the origin of severe acute respiratory...
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Background The etiology of many genetic diseases is challenging. This is especially true for developmental disorders of the central nervous system, since several genes can be involved. Many of such pathologies are considered rare diseases, since they affect less than 1 in 2000 people. Due to their low frequency, they present several difficulties fo...
Preprint
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Background: Uruguay is one of the few countries in the Americas that successfully contained the COVID-19 epidemic during the first half of 2020. Nevertheless, the intensive human mobility across the dry border with Brazil is a major challenge for public health authorities. We aimed to investigate the origin of SARS-CoV-2 strains detected in Uruguay...
Preprint
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The Archaea present profound differences compared to Bacteria in fundamental molecular and cellular processes. While most Archaea divide by binary fission using an FtsZ-based system similar to Bacteria, they lack the majority of the components forming the complex bacterial divisome. Moreover, how FtsZ precisely functions and interacts with other pr...
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The mechanisms of Z-ring assembly and regulation in bacteria are poorly understood, particularly in non-model organisms. Actinobacteria, a large bacterial phylum that includes the pathogen Mycobacterium tuberculosis, lack the canonical FtsZ-membrane anchors and Z-ring regulators described for E. coli. Here we investigate the physiological function...
Preprint
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The mechanisms of Z-ring assembly and regulation in bacteria are poorly understood, particularly in non-model organisms. Actinobacteria, one of the largest bacterial phyla that includes the deadly human pathogen Mycobacterium tuberculosis, lack the canonical FtsZ-membrane anchors as well as all positive and negative Z-ring regulators described for...
Article
Mitochondrial diseases (MD) are a group of diseases that can be caused by either mutations in the mitochondrial genome or nuclear DNA. MD may be difficult to diagnose since very often they are highly heterogeneous and with overlapping phenotypes. Molecular genomics approaches, especially NGS have helped in this sense. In this study we have sequence...
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Bacterial kinesin light chain is a TPR domain-containing protein encoded by the bklc gene, which co-localizes with the bacterial tubulin (btub) genes in a conserved operon in Prosthecobacter. Btub heterodimers show high structural homology with eukaryotic tubulin and assemble into head-to-tail protofilaments. Intriguingly, Bklc is homologous to the...
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We previously reported a multigene family of monodomain Kunitz proteins from Echinococcus granulosus (EgKU-1-EgKU-8), and provided evidence that some EgKUs are secreted by larval worms to the host interface. In addition, functional studies and homology modeling suggested that, similar to monodomain Kunitz families present in animal venoms, the E. g...
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Cell–cell fusion is inherent to sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in diverse organisms, but their exact role is unclear. In this study, we show that Arabidopsis thaliana HAP2/GCS1 is sufficient to promote mammalian cell–cell fusion. Hemifusion and complete fusion...
Preprint
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Cell-cell fusion is inherent to any form of sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in different organisms but their exact role is unclear. Here we show that Arabidopsis HAP2/GCS1 expression in mammalian cells is sufficient to promote cell-cell fusion. Hemifusion and co...
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Gli2 is the primary transcriptional activator of Hedgehog signalling in mammals. Upon stimulation of the pathway, Gli2 moves into the cilium before reaching the nucleus. However, the mechanisms underlying its entry into the cilium are not completely understood. Since several similarities have been reported between nuclear and ciliary import, we inv...
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The genus Leptospira is composed of pathogenic and saprophytic spirochetes. Pathogenic Leptospira is the etiological agent of leptospirosis, a globally spread neglected disease. A key ecological feature of some pathogenic species is their ability to survive both within and outside the host. For most leptospires, the ability to persist outside the h...
Article
Mitochondrial diseases are a group of clinically heterogeneous disorders that can be difficult to diagnose. We report a two and a half years old girl with clinical symptoms compatible with Leigh disease but with no definitive diagnosis. Using next generation sequencing we found that mutation 3697G>A was responsible for the patient’s clinical sympto...
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Aims: Members of the thioredoxin (Trx) protein family participate mainly in redox pathways and have not been associated with Fe/S binding, in contrast to some closely related glutaredoxins (Grxs). Cestode parasites possess an unusual diversity of Trxs and Trx-related proteins with non-explored functions. Here we addressed the biochemical character...
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Dendrotoxins are a group of peptide toxins purified from the venom of several mamba snakes. α-dendrotoxin (α-DTx, from the Eastern green mamba Dendroaspis angusticeps) is a well-known blocker of voltage-gated K(+) channels and specifically of Kv1.1, Kv1.2 and Kv1.6. In this work we show that α-DTx inhibited the ASIC currents in DRG neurons (IC50 =...
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Oxidative stress and iron limitation represent the grim side of life in an oxygen-rich atmosphere. The versatile electron transfer shuttle ferredoxin, an iron-sulfur protein, is particularly sensitive to these hardships, and its down-regulation under adverse conditions severely compromises survival of phototrophs. Replacement of ferredoxin by a str...
Article
PknG from Mycobacterium tuberculosis is a Ser/Thr protein kinase that regulates key metabolic processes within the bacterial cell as well as signaling pathways from the infected host cell. This multi-domain protein has a conserved canonical kinase domain with N- and C-terminal flanking regions of unclear functional roles. The N-terminus harbors a r...
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Cystathionine β-synthase (CBS) catalyzes the condensation of homocysteine with serine or cysteine to form cystathionine and H 2 O or H 2 S. Human CBS has a non-catalytic heme bound to cysteine and histidine. The heme environment is conserved among several eukaryotic species but does not resemble any other protein. Fe(III)-CBS is relatively unreacti...
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Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder that is generally inherited in an autosomal recessive fashion. However, in some families, trans mutant alleles interact with the primary causal locus to modulate the penetrance and/or the expressivity of the phenotype. CCDC28B (MGC1203) was identified as a second site modifier of B...
Chapter
A plausible route to highly concentrated cellular compartments is sketched. The main driving force comes from the selective advantage of a higher macromolecular content. The evolution from a diluted to a crowded state is described with a minimal model of growing bacteria. Additional simplifications to the model, aimed to mimic ancestral protocellul...
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We present a method that identifies associations between amino acid changes in potentially significant sites in an alignment (taking into account several amino acid properties) with phenotypic data, through the phylogenetic mixed model. The latter accounts for the dependency of the observations (organisms). It is known from previous studies that th...
Article
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Eisosomes define sites of plasma membrane organization. In Saccharomyces cerevisiae, eisosomes delimit furrow-like plasma membrane invaginations that concentrate sterols, transporters, and signaling molecules. Eisosomes are static macromolecular assemblies composed of cytoplasmic proteins, most of which have no known function. In this study, we use...
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DesK is a sensor histidine kinase (HK) that allows Bacillus subtilis to respond to cold shock, triggering the adaptation of membrane fluidity via transcriptional control of a fatty acid desaturase. It belongs to the HK family HPK7, which includes the nitrogen metabolism regulators NarX/Q and the antibiotic sensor LiaS among other important sensor k...
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Risk factors discovery and prevention is an active research field within the biomedical domain. Despite abundant existing information on risk factors, as found in bibliographical databases or on several websites, accessing this information may be difficult. Methods from Natural Language Processing and Information Extraction can be helpful to access...
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The gene Rv2714 from Mycobacterium tuberculosis, which codes for a hypothetical protein of unknown function, is a representative member of a gene family that is largely confined to the order Actinomycetales of Actinobacteria. Sequence analysis indicates the presence of two paralogous genes in most mycobacterial genomes and suggests that gene duplic...
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The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross...
Article
We investigated the ability of the most common TCR-gamma and delta chains to express on the cell surface. Vgamma1Cgamma4 and Vgamma7Cgamma1 chains paired with all TCR-delta chains tested, whereas Vgamma4Cgamma1 chains were found with Vdelta4 and Vdelta5, but not with Vdelta2 or Vdelta6 chains, and Vgamma2Cgamma2 chains were expressed only with Vdel...
Article
Cystathionine beta-synthase (CBS) catalyzes the condensation of serine and homocysteine to cystathionine, which represents the committing step in the transsulfuration pathway. CBS is unique in being a pyridoxal phosphate-dependent enzyme that has a heme cofactor. The activity of CBS under in vitro conditions is responsive to the redox state of the...
Article
Reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes, not only in eukaryotes but also in bacteria. A growing body of evidence suggests that Ser/Thr phosphorylation play important roles in the physiology and virulence of Mycobacterium tuberculosis, the etiological agent of tuberculosis. This pathogen...
Article
Mycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTase). As part of a Structural Genomics initiative on conserved hypothetical proteins in pathogenic mycobacteria, we ha...
Article
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The gene Rv0813c from Mycobacterium tuberculosis, which codes for a hypothetical protein of unknown function, is conserved within the order Actinomycetales but absent elsewhere. The crystal structure of Rv0813c reveals a new family of proteins that resemble the fatty acid-binding proteins (FABPs) found in eukaryotes. Rv0813c adopts the 10-stranded...
Article
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Contemporary cells show a highly crowded macromolecular content, the processes which originated this state being largely unknown. We propose that a driving force leading to the crowded cellular state could be the increase in growth rate produced by an enhanced cytoplasmic protein concentration. Briefly, in a diluted scenario, an increase in protein...
Article
The crystal structure of Mycobacterium tuberculosis adenylate kinase (MtAK) in complex with two ADP molecules and Mg2+ has been determined at 1.9 A resolution. Comparison with the solution structure of the enzyme, obtained in the absence of substrates, shows significant conformational changes of the LID and NMP-binding domains upon substrate bindin...
Article
Full-text available
The gene Rv0813c from Mycobacterium tuberculosis, which codes for a hypothetical protein of unknown function, is conserved within the order Actinomycetales but absent elsewhere. The crystal structure of Rv0813c reveals a new family of proteins that resemble the fatty acid-binding proteins (FABPs) found in eukaryotes. Rv0813c adopts the 10-stranded...
Article
Full-text available
Laboratory experiments under controlled conditions during thousands of generations are useful tools to assess the processes underlying bacterial evolution. As a result of these experiments, the way in which the traits change in time is obtained. Under these conditions, the bacteria E. coli shows a parallel increase in cell volume and fitness. To ex...

Projects

Projects (5)
Project
Long-lasting project aimed to characterize the structural basis of glutaredoxin and other thioredoxin-fold proteins mechanism and selectivity. Focus on comparing human and pathogenic homologues to unravel lineage-specific variations in pathogenic species.