Referencia

Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15372-7

Autores

Fillet S, Krell T, Morel B, Lu D, Zhang X, Ramos JL.

Resumen

Members of the IclR family control bacterial genes involved in a number of physiological processes. The IclR-family member TtgV crystallizes as a tetramer, with each TtgV monomer consisting of two domains--a DNA binding domain and an effector recognition domain, which are interconnected by an extended α-helix. When bound to DNA, a kink is introduced so that the extended helix is split in two α-helices (helix-4 and -5). Differential scanning calorimetry studies revealed that TtgV unfolds in a single event, suggesting that the two domains unfold cooperatively. When mutations are introduced in helix-5 that disrupt interactions between Arg98 and Glu102, the thermal unfolding of the TtgV domains becomes uncoupled without compromising effector binding. Two of these mutants (TtgVE102R and TtgVE102A) showed impaired release from target DNA, suggesting that these mutations alter signal transmission. By combining various mutants, we found that the mutations in the connecting α-helix exhibited a dominant effect over mutations in DNA binding and effector binding domains. We propose a model in which the loss of cooperativity of unfolding of TtgV reflects perturbed interdomain communication, and that the transition from the continuous to discontinuous helix may mediate interdomain communication necessary for the proper functioning of TtgV.

Descripción

El estudio del mayor regulador de resistencia a disolventes orgánicos de Pseudomonas putida DOT-T1E ha puesto en evidencia la importancia de la comunicación intra-molecular para el funcionamiento de una misma proteína. El represor TtgV funciona de manera cooperativa gracias a una larga hélice-α uniendo sus dominios de unión al ADN y de unión al ligando.

Foto grupo Noviembre

REFERENCIA DEL GRUPO E INVESTIGADOR
Contribuir a la lucha contra la contaminación medioambiental con la ayuda de herramientas biológicas. Los compuestos a combatir son hidrocarburos aromáticos (benceno, tolueno, etilbenceno y xilenos), nitroaromáticos como el TNT, haloaromáticos como los PCBs y pesticidas como el lindano y el DDT. El enfoque experimental incluye técnicas moleculares y el análisis bioquímico y genético de las rutas catabólicas, poniendo especial énfasis en las interacciones ADN/regulador, en experimentos en reactores y en la llamada rizorremediación de suelos. Sandy Fillet es microbióloga licenciada por la Universidad de Marsella y Doctora por la Universidad de Granada. Ha trabajado en el grupo del Dr. Ramos en el CSIC durante 5 años.

Descárgate este artículo aquí.
Más artículos en la revista SEBBM.

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio al mejor artículo de jóvenes de la SEBBM, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis

25-04-2021

Chronic kidney disease (CKD) remains a major epidemiological, clinical, and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) present a persistent inflammatory and profibrotic response. Fatty acid oxidation (FAO)...

Leer más

Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development

29-03-2021

Presynaptic spike timing-dependent long-term depression (t-LTD) at hippocampal CA3-CA1 synapses is evident until the 3rd postnatal week in mice, disappearing during the 4th week. At more mature stages, we found...

Leer más

Ceramide chain length–dependent protein sorting into selective endoplasmic reticulum exit sites

22-02-2021

Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport...

Leer más

Antigen retrieval and clearing for whole-organ immunofluorescence by FLASH

25-01-2021

Advances in light-sheet and confocal microscopy now allow imaging of cleared large biological tissue samples and enable the 3D appreciation of cell and protein localization in their native organ environment...

Leer más

Viral Bcl2s' transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis

08-01-2021

Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis...

Leer más

Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFß after myocardial infarction

01-12-2020

Macrophages (Mφs) produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these factors crosstalk with other cell types mediating repair is not fully understood...

Leer más

Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics

30-10-2020

Heteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic...

Leer más

Mechanisms of autoregulation of C3G, activator of the GTPase Rap1, and its catalytic deregulation in lymphomas

01-10-2020

C3G is a guanine nucleotide exchange factor (GEF) that regulates cell adhesion and migration by activating the GTPase Rap1. The GEF activity of C3G is stimulated by the adaptor proteins...

Leer más

Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia

31-08-2020

The reciprocal translocation t(12;21)(p13;q22)[ETV6/RUNX1] is the most frequent chromosomal rearrangement in pediatric B-cell acute lymphoblastic leukemia(B-ALL). Long non-coding RNAs (lncRNAs) play important roles in numerous diseases and they represent an...

Leer más

Evaluation of different approaches used to study membrane permeabilization by actinoporins on model lipid vesicles

30-07-2020

Release of aqueous contents from model lipid vesicles has been a standard procedure to evaluate pore formation efficiency by actinoporins, such as sticholysin II (StnII), for the last few decades...

Leer más

Socios Protectores