Browsing by Author "Perez Acle, Tomas"

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    A novel adrenocorticotropin receptor mutation alters its structure and function, causing familial glucocorticoid deficiency
    (ENDOCRINE SOC, 2008) Artigas, Rocio A.; Gonzalez, Angel; Riquelme, Erick; Carvajal, Cristian A.; Cattani, Andreina; Martinez Aguayo, Alejandro; Kalergis, Alexis M.; Perez Acle, Tomas; Fardella, Carlos E.
    Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by unresponsiveness to ACTH. In this study, two mutations of the ACTH receptor (MC2R) gene are reported in this FGD clinical case.
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    Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation
    (OXFORD UNIV PRESS, 2009) Ines Barria, Maria; Gonzalez, Angel; Vera Otarola, Jorge; Leon, Ursula; Vollrath, Valeska; Marsac, Delphine; Monasterio, Octavio; Perez Acle, Tomas; Soza, Alejandro; Lopez Lastra, Marcelo
    The HCV internal ribosome entry site (IRES) spans a region of similar to 340 nt that encompasses most of the 5' untranslated region (5'UTR) of the viral mRNA and the first 24-40 nt of the core-coding region. To investigate the implication of altering the primary sequence of the 5'UTR on IRES activity, naturally occurring variants of the 5'UTR were isolated from clinical samples and analyzed. The impact of the identified mutations on translation was evaluated in the context of RLuc/FLuc bicistronic RNAs. Results show that depending on their location within the RNA structure, these naturally occurring mutations cause a range of effects on IRES activity. However, mutations within subdomain IIId hinder HCV IRES-mediated translation. In an attempt to explain these data, the dynamic behavior of the subdomain IIId was analyzed by means of molecular dynamics (MD) simulations. Despite the loss of function, MD simulations predicted that mutant G266A/G268U possesses a structure similar to the wt-RNA. This prediction was validated by analyzing the secondary structure of the isolated IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg2+ ions. These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation.
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    Stochastic simulation of multiscale complex systems with PISKaS : a rule-based approach
    (2018) Perez Acle, Tomas; Fuenzalida, Ignacio; Martin, Alberto J.M.; Santibáñez Palominos, Rodrigo Alberto; Avaria, Rodrigo; Bernardin, Alejandro; Bustos, Alvaro M.; Garrido Cortés, Daniel; Dushoff, Jonathan; Liu, James H.
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    Structure-function relationship between the tobamovirus TMV-Cg coat protein and the HR-like response
    (MICROBIOLOGY SOC, 2008) Ehrenfeld, Nicole; Gonzalez, Angel; Canon, Paola; Medina, Consuelo; Perez Acle, Tomas; Arce Johnson, Patricio
    The tobamovirus TMV-Cg induces an HR-like response in Nicotiana tabacum cv. Xanthi nn sensitive plants lacking the N or N' resistance genes. This response has been characterized by the appearance of necrotic lesions in the inoculated leaf and viral systemic spread, although the defence pathways are activated in the plant. A previous study demonstrated that the coat protein (CP) of TMV-Cg (CPCg) was the elicitor of this HR-like response. We examined the influence of four specific amino acid substitutions on the structure of CPCg, as well as on the development of the host response. To gain insights into the structural implications of these substitutions, a set of molecular dynamic experiments was performed using comparative models of wild-type and mutant CPCg as well as the CP of the U1 strain of TMV (CPU1), which is not recognized by the plants. A P21L mutation produces severe changes in the three-dimensional structure of CPCg and is more unstable when this subunit is laterally associated in silico. This result may explain the observed incapacity of this mutant to assemble virions. Two other CPCg mutations (R46G and S54K) overcome recognition by the plant and do not induce an HR-like response. A double CPCg mutant P21L-S54K recovered its capacity to form virions and to induce an HR-like response. Our results suggest that the structural integrity of the CP proteins is important for triggering the HIR-like response.
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    The N-homologue LRR domain adopts a folding which explains the TMV-Cg-induced HR-like response in sensitive tobacco plants
    (ELSEVIER SCIENCE INC, 2008) Stange, Claudia; Matus, Jose Tomas; Dominguez, Calixto; Perez Acle, Tomas; Arce Johnson, Patricio
    Following leaf infection with the tobacco mosaic virus (TMV), Nicotiana species that carry the disease resistance N gene develop a hypersensitive response (HR) that blocks the systemic movement of the virus. TMV-sensitive tobacco plants that lack the N gene develop classical disease symptoms following infection with most of the tobamoviruses. However, upon infection with TMV-Cg, these p, ants display a HR-like response that is unable to limit viral spread. We previously identified the NH gene in sensitive plants; this gene is homologous to the resistance N gene and both belong to the TIR/NBS/LRR family. Isolation and analysis of the NH transcript enabled the prediction of the amino acid sequence in which we detected a leucine-rich repeat domain, proposed to be involved in pathogen recognition. This domain is found in four of five classes of pathogen resistant proteins, in which sequence and structural changes may generate different specificities. In order to study the possible functional role of the LRR domain in the HR-like response, we developed a comparative three-dimensional model for the NH and N gene products, by means of functional and structural domains recognition, secondary structure prediction, domain assignment through profile Hidden Markov Models (HMM) and molecular dynamics (MD) simulations. Based on our results we postulate that the NH protein could adopt a LRR fold with a functional role in the HR-like response. Our two reliable LRR three-dimensional models (N-LRR, NH-LRR) can be used as structural frameworks for future experiments in which the structure-function relationships regarding the protein-protein interaction process may be revealed. Evolutionary aspects of the N and NH genes in Nicotiana species are also discussed. (c) 2007 Elsevier Inc. All rights reserved.