196,676 research outputs found
Impulso de cultura emprendedora en estudiantes de la Facultad de Ciencias a través de la dinamización de prácticas externas
No full textMemoria ID-0145. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017
The Roco protein family: a functional perspective
No full textIn this review, we discuss the evolutionary, biochemical, and functional data available for members of the Roco protein family. They are characterized by having a conserved supradomain that contains a Ras-like GTPase domain, called Roc, and a characteristic COR (C-terminal of Roc) domain. A kinase domain and diverse regulatory and protein protein interaction domains are also often found in Roco proteins. First detected in the slime mold Dictyostelium discoideum, they have a broad phylogenetic range, being present in both prokaryotes and eukaryotes. The functions of these proteins are diverse. The best understood are Dictyostelium Rocos, which are involved in cell division, chemotaxis, and development. However, this family has received extensive attention because mutations in one of the human Roco genes (LRRK2) cause familial Parkinson disease. Other human Rocos are involved in epilepsy and cancer. Biochemical data suggest that Roc domains are capable of activating kinase domains intramolecularly. Interestingly, some of the dominant, disease-causing mutations in both the GTPase and kinase domains of LRRK2 increase kinase activity. Thus, Roco proteins may act as stand-alone transduction units, performing roles that were thought so far to require multiple proteins, as occur in the Ras transduction pathway
Characterization of the Roco Protein Family in Dictyostelium discoideum
No full textThe Roco family consists of multidomain Ras-GTPases that include LRRK2, a protein mutated in familial Parkinson’s disease. The genome of the cellular slime mold Dictyostelium discoideum encodes 11 Roco proteins. To study the functions of these proteins, we systematically knocked out the roco genes. Previously described functions for GbpC, Pats1, and QkgA (Roco1 to Roco3) were confirmed, while novel developmental defects were identified in roco4- and roco11-null cells. Cells lacking Roco11 form larger fruiting bodies than wild-type cells, while roco4-null cells show strong developmental defects during the transition from mound to fruiting body; prestalk cells produce reduced levels of cellulose, leading to unstable stalks that are unable to properly lift the spore head. Detailed phylogenetic analysis of four slime mold species reveals that QkgA and Roco11 evolved relatively late by duplication of an ancestor roco4 gene (later than ~300 million years ago), contrary to the situation with other roco genes, which were already present before the split of the common ancestor of D. discoideum and Polysphondylium pallidum (before ~600 million years ago). Together, our data show that the Dictyostelium Roco proteins serve a surprisingly diverse set of functions and highlight Roco4 as a key protein for proper stalk cell formation.
RoCo : a physically animated desktop computer for ergonomic and affective movement
No full textThesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2006.Includes bibliographical references (leaves 83-84).For better or worse, more people are spending their days in front of computers. With this increase in computer use, more people are complaining of back and neck pain. The simple act of changing your posture, however, can dramatically reduce the risk of back or neck injury from prolonged computer use. RoCo, the robotic computer, can encourage computer users to change posture by moving its screen to different positions. Having introduced motion, RoCo can now also begin to build a social relationship with the user and affect his affective state. This thesis describes the workings of RoCo and the results of an initial user study to produce affective movement.by Andrew Wang.M.Eng
Biochemical and kinetic properties of the complex Roco G-protein cycle
No full textRoco proteins have come into focus after mutations in the gene coding for the human Roco protein Leucine-rich repeat kinase 2 (LRRK2) were discovered to be one of the most common genetic causes of late onset Parkinson's disease. Roco proteins are characterized by a Roc domain responsible for GTP binding and hydrolysis, followed by a COR dimerization device. The regulation and function of this RocCOR domain tandem is still not completely understood. To fully biochemically characterize Roco proteins, we performed a systematic survey of the kinetic properties of several Roco protein family members, including LRRK2. Together, our results show that Roco proteins have a unique G-protein cycle. Our results confirm that Roco proteins have a low nucleotide affinity in the micromolar range and thus do not strictly depend on G-nucleotide exchange factors. Measurement of multiple and single turnover reactions shows that neither Pi nor GDP release are rate-limiting, while this is the case for the GAP-mediated GTPase reaction of some small G-proteins like Ras and for most other high affinity Ras-like proteins, respectively. The KM values of the reactions are in the range of the physiological GTP concentration, suggesting that LRRK2 functioning might be regulated by the cellular GTP level
The unconventional G-protein cycle of LRRK2 and Roco proteins
No full textMutations in the human leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of hereditary Parkinson's disease (PD). LRRK2 belongs to the Roco family of proteins, which are characterized by the presence of a Ras of complex proteins domain (Roc), a C-terminal of Roc domain (COR) and a kinase domain. Despite intensive research, much remains unknown about activity and the effect of PD-associated mutations. Recent biochemical and structural studies suggest that LRRK2 and Roco proteins are noncanonical G-proteins that do not depend on guanine nucleotide exchange factors or GTPase-activating proteins for activation. In this review, we will discuss the unusual G-protein cycle of LRRK2 in the context of the complex intramolecular LRRK2 activation mechanism
Procedimientos de apoyo para la realización del seguimiento del título de grado en física
No full textMemoria ID11-082. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2011-2012.Este proyecto está relacionado con los protocolos para el seguimiento y renovación de
la acreditación de títulos universitarios oficiales, que tienen como objetivo completar la
implantación de los mismos y analizar sus resultados.
Los objetivos de este seguimiento han sido establecidos por la CURSA (Comisión
Universitaria para la Regulación del Seguimiento y la Acreditación, creada por Consejo
de Universidades y la Conferencia General de Política Universitaria) y son los
siguientes:
- Dotar de visibilidad y transparencia al proyecto y desarrollo del título.
- Cumplir los objetivos planteados y adquiridos en la propuesta del plan de
estudios.
- Proporcionar recomendaciones y sugerencias de mejora.
Estos han sido por tanto los objetivos que para el Grado en Física se asumen en el
presente proyecto de innovación docente
Actividades de difusión y promoción para el nuevo Máster Universitario en Física y Matemáticas
No full textMemoria ID-0225. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2015-2016
Structure and nucleotide-induced conformational dynamics of the Chlorobium tepidum Roco protein
No full textThe LRR-Roc-COR domains are central to the action of nearly all Roco proteins, including the Parkinson's disease-associated protein LRRK2. We previously demonstrated that the Roco protein from Chlorobium tepidum (CtRoco) undergoes a dimer-monomer cycle during the GTPase reaction, with the protein being mainly dimeric in the nucleotide-free and GDP-bound states and monomeric in the GTP-bound state. Here, we report a crystal structure of CtRoco in the nucleotide-free state showing for the first time the arrangement of the LRR-Roc-COR. This structure reveals a compact dimeric arrangement and shows an unanticipated intimate interaction between the Roc GTPase domains in the dimer interface, involving residues from the P-loop, the switch II loop, the G4 region and a loop which we named the "Roc dimerization loop". Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) is subsequently used to highlight structural alterations induced by individual steps along the GTPase cycle. The structure and HDX-MS data propose a pathway linking nucleotide binding to monomerization and relaying the conformational changes via the Roc switch II to the LRR and COR domains. Together, this work provides important new insights in the regulation of the Roco proteins
- …
