The Structural Genomic Group develops structural studies by X-ray diffraction of proteins and protein interactions involved in the innate immune response and a number of different prokaryote proteins that are targets for health and biotechnological applications, using a structural genomic approach.
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Maria Arménia Carrondo
The main goals of the Structural Genomics Group is to study eukaryotic proteins that are involved in the innate immune response, viral latency, as well as prokaryotic proteins that are targets for health and biotechnological applications and proteins that are involved on the oxidative stress response, using a structural genomics approach.
Toll-like receptors (TLRs) and NOD-like receptors (NLRs) and their role in pathogen recognition is one the family being studied. They have been implicated in protective immune responses elicited by intracellular pathogens or endogenous danger signals. Our aim is to understand the protein interactions and modes of binding within signal transduction and regulation of NOD2 activation and the role of pathogen recognition by TLR9 in the innate immune response. Grim19 is one of our objective of study by itself and also because it interacts with some domains of NOD2. It is localized in the mitochondria as a component of the NADH:ubiquinone oxidoreductase (complex I) and it has been shown to trigger cell apoptosis. Grim19 is associated with tumorigenesis and it has been demonstrated that some oncogenic proteins bind and inactivate it.
We are also addressing the crystal structure determination of the M2 and mORF73 proteins encoded by the murid gamma-herpesvirus 4 to understand their structural role in viral latency. A hallmark of herpesvirus infection is the establishment of lifelong latency in the host, which is associated with the different malignancies caused by the gamma-herpesviruses.
Our research is also dedicated to the study of proteins from prokaryotes. In particular, we are interested in the mechanism of cleavage of glycosidic bonds of glycoside hydrolases and in the mechanism of dioxygen reduction to water by multi-copper oxidases. We also study metalloproteins from the radiation resistant bacterium Deinococcus radiodurans and proteins related with oxidative stress which belong to different families: proteins which protect DNA under stress conditions (Dps) and proteins that detoxify oxygen reactive species such as superoxide anion (superoxide reductase and superoxide dismutase) or hydrogen peroxide (rubrerythrins).
- S. Gonçalves, S. P. Miller, M. A. Carrondo, A. M. Dean and P. M.
Matias, "Induced Fit and the Catalytic Mechanism of Isocitrate
Dehydrogenase", Biochemistry (2012), 51:7098–7115
- S. Gorynia, T. M. Bandeiras, F. G. Pinho, C. E. McVey, C. Vonrhein, A.
Round, D. I. Svergun, P. Donner, P. M. Matias and M. A. Carrondo
“Structural and functional insights into a dodecameric molecular machine
– The RuvBL1/RuvBL2 complex”, J. Struct. Biol. (2011), 176, 279-291.
- C. M. Romão, D. Ladakis, S. A. L. Lobo, M. A. Carrondo, A. A.
Brindley, E. Deery, P. M. Matias, R. W. Pickersgill, L. M. Saraiva and
M. J. Warren “ Evolution in a family of chelatases facilitated by the
introduction of active site assymmentry and protein ologomerisation”
PNAS (2011) 108, 97-102.
MX Unit Website
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Unidade de Cristalografia de Macromoléculas
O laboratório de Genómica Estrutural tem como objectivo a determinação da estrutura por difracção de raios X de proteínas relacionadas com a saúde humana e as suas aplicações bioquímicas. Estamos particularmente interessados nos receptores do tipo "NOD-like receptors", e no seu papel no reconhecimento de agentes patogénicos. Estes receptores desempenham um papel fundamental na resposta do sistema imunitário a agentes deste tipo e no nosso laboratório procuramos as bases moleculares e estruturais que estão subjacentes à interacção destes receptores com outras proteínas que integram os mecanismos de transdução de sinal. Simultaneamente também determinamos as bases moleculares de mecanismos enzimáticos de metaloenzimas e sua função, nomeadamente os mecanismos enzimáticos das oxidases de multi-cobre, das hidrolases glicosídicas e de um certo número de proteínas da bactéria Deinococcus radiodurans, que é uma bactéria muito resistente à radiação, a dessecação, e a várias outras condições de stress.