Publication: Interacciones de proteína-péptido: estudio de DYLLT1 y del dominio PDZ de la Óxido Nítrico Sintasa neuronal
Loading...
Official URL
Full text at PDC
Publication Date
2017-05-09
Authors
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad Complutense de Madrid
Citations
Exportar
Abstract
Las interacciones entre proteínas son un proceso fundamental para la organización de las estructuras biológicas. La formación de complejos proteicos sirve para regular las actividades enzimáticas, organizar espacio-temporalmente las respuestas celulares a estímulos, proporcionar forma, movimiento y comunicación a las células o dirigir el transporte intracelular de orgánulos. En definitiva, todas las funciones celulares dependen de las interacciones entre sus proteínas. La pérdida de estas interacciones conlleva a la deslocalización de sus miembros, el desacoplamiento de sistemas que deben actuar en conjunto, o la desregulación de los mecanismos de control, lo que se traduce en un estado patológico. En esta Memoria se recogen los experimentos enfocados en la caracterización de dos elementos importantes para la formación de complejos proteicos y redes de interacción con profundas implicaciones biológicas. Por un lado se ha estudiado el dominio PDZ de la nNOS, el cual es un elemento estructural y funcional exclusivo de esta isoforma, y sirve para asociarse a grandes complejos proteicos. El óxido nítrico ( NO) es un señalizador celular sintetizado por las enzimas NOS, que está cobrando cada vez más importancia por sus acciones a nivel vascular, neuronal e inmunológico y por su implicación en patologías y enfermedades. Debido a la naturaleza difusible y reactiva del NO, su síntesis tiene que estar restringida al momento y al lugar adecuado, y además de los mecanismos de regulación generales a nivel catalítico presentes en las NOSs, la nNOS puede tener un factor adicional de regulación controlando su localización subcelular gracias al dominio PDZ que presenta en su extremo N-terminal. Los dominios PDZ (de PSD-95, DlgA, ZO1) son módulos estructurales que median la formación de complejos, y pueden estar aislados o en tándem para esta tarea. Tienen unos 90 aminoácidos que se distribuyen en seis cadenas b (1 a 6) y dos hélices a. Hay que destacar el lazo de unión del grupo carboxilato, que conecta las hebras b1 y 2, y reconoce específicamente el grupo carboxilato del extremo C-terminal del ligando...
Protein interactions are fundamental processes for the organization of the biological structures. Protein complexes are assembled during the regulation of enzymatic activities, the spatial and temporal organization of cell responses, mediate movement and communication between cells, direct the intracellular transport of cell organelles and the regulation of every single cellular function is dependent of the interrelationships of several proteins. Loss of these interactions means the misslocalization of their members, the uncoupling of the systems that act together or the disregulation of control mechanisms hence leading to pathologies. This Dissertation assesses the characterization of two important elements in the assembly of large protein complexes and interaction networks, both of them with profound biological implications. On the one hand, the PDZ domain of neuronal Nitric Oxide Synthase (nNOS) was studied, which is an exclusive element of this NOS isoform, and it drives the association of nNOS to the protein complexes where it exerts its function. Nitric oxide is a small signaling molecule synthetized by the NOSs enzymes. It is becoming increasingly relevant, because it has important functions in neural, vascular and immunological physiology, and it has been implicated in pathologies and diseases. Due to its highly diffusible and reactive nature, NO has a highly regulated synthesis in a spatial and temporal manner, and in addition to the general regulation of the catalytic activity of NOSs, nNOS in particular has an added point of regulation by the control of its subcellular localization, thanks to the presence of the PDZ domain at its N-terminus...
Protein interactions are fundamental processes for the organization of the biological structures. Protein complexes are assembled during the regulation of enzymatic activities, the spatial and temporal organization of cell responses, mediate movement and communication between cells, direct the intracellular transport of cell organelles and the regulation of every single cellular function is dependent of the interrelationships of several proteins. Loss of these interactions means the misslocalization of their members, the uncoupling of the systems that act together or the disregulation of control mechanisms hence leading to pathologies. This Dissertation assesses the characterization of two important elements in the assembly of large protein complexes and interaction networks, both of them with profound biological implications. On the one hand, the PDZ domain of neuronal Nitric Oxide Synthase (nNOS) was studied, which is an exclusive element of this NOS isoform, and it drives the association of nNOS to the protein complexes where it exerts its function. Nitric oxide is a small signaling molecule synthetized by the NOSs enzymes. It is becoming increasingly relevant, because it has important functions in neural, vascular and immunological physiology, and it has been implicated in pathologies and diseases. Due to its highly diffusible and reactive nature, NO has a highly regulated synthesis in a spatial and temporal manner, and in addition to the general regulation of the catalytic activity of NOSs, nNOS in particular has an added point of regulation by the control of its subcellular localization, thanks to the presence of the PDZ domain at its N-terminus...
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular I, leída el 28/06/2016