Fundación Instituto Leloir

About: Fundación Instituto Leloir is a facility organization based out in Buenos Aires, Argentina. It is known for research contribution in the topics: Dentate gyrus & Neurogenesis. The organization has 702 authors who have published 1052 publications receiving 39299 citations.

Targeting mechanism of the retinoblastoma tumor suppressor by a prototypical viral oncoprotein. Structural modularity, intrinsic disorder and phosphorylation of human papillomavirus E7.

Abstract: DNA tumor viruses ensure genome amplification by hijacking the cellular replication machinery and forcing infected cells to enter the S phase. The retinoblastoma (Rb) protein controls the G1/S checkpoint, and is targeted by several viral oncoproteins, among these the E7 protein from human papillomaviruses (HPVs). A quantitative investigation of the interaction mechanism between the HPV16 E7 protein and the RbAB domain in solution revealed that 90% of the binding energy is determined by the LxCxE motif, with an additional binding determinant (1.0 kcal·mol−1) located in the C-terminal domain of E7, establishing a dual-contact mode. The stoichiometry and subnanomolar affinity of E7 indicated that it can bind RbAB as a monomer. The low-risk HPV11 E7 protein bound 2.0 kcal·mol−1 more weakly than the high-risk HPV16 and HPV18 type counterparts, but the modularity and binding mode were conserved. Phosphorylation at a conserved casein kinase II site in the natively unfolded N-terminal domain of E7 affected the local conformation by increasing the polyproline II content and stabilizing an extended conformation, which allowed for a tighter interaction with the Rb protein. Thus, the E7–RbAB interaction involves multiple motifs within the N-terminal domain of E7 and at least two conserved interaction surfaces in RbAB. We discussed a mechanistic model of the interaction of the Rb protein with a viral target in solution, integrated with structural data and the analysis of other cellular and viral proteins, which provided information about the balance of interactions involving the Rb protein and how these determine the progression into either the normal cell cycle or transformation. Structured digital abstract • MINT-7383794, MINT-7383812, MINT-7383830, MINT-7383868, MINT-7383891, MINT-7384056: E7 (uniprotkb:P03129) and Rb (uniprotkb:P06400) bind (MI:0407) by fluorescence technologies (MI:0051) • MINT-7383923: E7 (uniprotkb:P04020) and Rb (uniprotkb:P06400) bind (MI:0407) by competition binding (MI:0405) • MINT-7383777, MINT-7384078, MINT-7383848, MINT-7384113, MINT-7384096: Rb (uniprotkb:P06400) and E7 (uniprotkb:P03129) bind (MI:0407) by competition binding (MI:0405) • MINT-7383963: Rb (uniprotkb:P06400) and E7 (uniprotkb:P06788) bind (MI:0407) by competition binding (MI:0405) • MINT-7384022, MINT-7384040: E7 (uniprotkb:P03129) and Rb (uniprotkb:P06400) bind (MI:0407) by comigration in non denaturing gel electrophoresis (MI:0404) • MINT-7384004, MINT-7383984: Rb (uniprotkb:P06400) binds (MI:0407) to E7 (uniprotkb:P03129) by pull down (MI:0096)

Burkholderia puraquae sp. nov., a novel species of the Burkholderia cepacia complex isolated from hospital settings and agricultural soils

Abstract: Bacteria from the Burkholderia cepacia complex (Bcc) are capable of causing severe infections in patients with cystic fibrosis (CF). These opportunistic pathogens are also widely distributed in natural and man-made environments. After a 12-year epidemiological surveillance involving Bcc bacteria from respiratory secretions of Argentinean patients with CF and from hospital settings, we found six isolates of the Bcc with a concatenated species-specific allele sequence that differed by more than 3 % from those of the Bcc with validly published names. According to the multilocus sequence analysis (MLSA), these isolates clustered with the agricultural soil strain, Burkholderia sp. PBP 78, which was already deposited in the PubMLST database. The isolates were examined using a polyphasic approach, which included 16S rRNA, recA, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), DNA base composition, average nucleotide identities (ANIs), fatty acid profiles, and biochemical characterizations. The results of the present study demonstrate that the seven isolates represent a single novel species within the Bcc, for which the name Burkholderia puraquae sp. nov. is proposed. Burkholderia puraquae sp. nov. CAMPA 1040T (=LMG 29660T=DSM 103137T) was designated the type strain of the novel species, which can be differentiated from other species of the Bcc mainly from recA gene sequence analysis, MLSA, ANIb, MALDI-TOF MS analysis, and some biochemical tests, including the ability to grow at 42 °C, aesculin hydrolysis, and lysine decarboxylase and β-galactosidase activities.

Mmp1 processing of the PDF neuropeptide regulates circadian structural plasticity of pacemaker neurons.

Abstract: In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior.

Melatonin Inhibits Glucocorticoid Receptor Nuclear Translocation in Mouse Thymocytes

Abstract: The antiapoptotic effect of melatonin (MEL) has been described in several systems. In particular, MEL inhibits glucocorticoid-mediated apoptosis. Our group previously demonstrated that in the thymus, MEL inhibits the release of Cytochrome C from mitochondria and the dexamethasonedependent increase of bax mRNA levels. In this study we analyzed the ability of MEL to regulate the activation of the glucocorticoid receptor (GR) in mouse thymocytes. We found that even though the methoxyindole does not affect the ligand binding capacity of the receptor, it impairs the steroid-dependent nuclear translocation of the GR and also prevents transformation by blocking the dissociation of the 90-kDa heat shock protein. Coincubation of the methoxyindole with dexamethasone did not affect the expression of a reporter gene in GR-transfected Cos-7 cells or HC11 and L929 mouse cell lines that express Mel-1a and retinoid-related orphan receptor- (ROR) receptors. Therefore, the antagonistic effect of MEL seems to be specific for thymocytes, in a Mel 1a- and ROR-independent manner. In summary, the present results suggest a novel mechanism for the antagonistic action of MEL on GR-mediated effects, which involves the inhibition of 90kDa heat shock protein dissociation and the cytoplasmic retention of the GR. (Endocrinology 147: 5452–5459, 2006)