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The main interest of our group is the study of the mechanisms of molecular motors involved in DNA and protein transport across biological membranes. Our model system is the bacterial Type IV secretion system.

Bacterial Type IV Secretion Systems (T4SS) are sophistacated machineries involved in the transfer of genetic material in bacteria conjugation. Bacterial conjugation is essential for the widespread dissemination of antibiotic resistance genes. T4SS are also essential for pathogenic bacteria such as Helicobacter pylori, Legionella pneumophilla Yersinia pestis or Brucella abortus to deliver virulence effectors into eukaryotic cells. Hence, understanding the molecular basis or DNA and protein transport by T4SS is critical to develop drugs able to block these processes.

T4SS are large macromolecular assemblies formed by 11 different proteins, termed VirB1 to VirB11 in the nomenclature of Agrobacterium tumefaciens and a coupling protein (VirD4), involved in ssDNA transport among cells. Three of these proteins, VirB4, VirB11, and VirD4 are ATPases that provide the energy for pilus assembly and DNA/protein transport. These proteins are called TrwK, TrwD, and TrwB, respectively, in our system model, the conjugative plasmid R388.

Motor domains in DNA and protein translocases, such as the coupling protein TrwB, the chromosome segregation pump FtsK and VirB4 proteins, share a striking structural similarity. This motor domain seems to have evolved from a common evolutionary ancestor. Despite the variability in the biological functions, this motor domain perfoms alwsays the same function, consisting of converting the chemical energy of ATP hydrolysis into mechanical work.

We use a combination of genetic, biochemical, biophysical, and structural tools, which, in combination, help us to gather further understanding of the molecular mechanisms of these molecular motors. We share the facilities and also, and foremost, the ideas with the group of Prof. Fernando de la Cruz at the Department of Molecular Biology, in the Medical School of the Universidad de Cantabria. In the new future (ca. june 2013),we will move to the brand new facilties of the Instituto de Biomedicina y Biotecnología in the Science Park at the outskirts of Santander.

We also mantain a fruitful collaboration with the groups of Prof. J. L. Carrascosa and Prof. J. M. Valpuesta at the Centro Nacional de Biotecnología (CNB-CSIC, Madrid, Spain). They help us in our structural studies by Electron Microscopy. In addition, we collaborate with Dr.Borja Ibarra, at the Insituto Nacional de Nanociencias (IMDEA, Madrid, Spain). for single molecule studies with optical tweezers, and Prof. Miquel Coll at the Instituto de Investigación Biomédica (IRB Barcelona, Spain) for protein crystalography.

Architecture of a Type IV secretion system

DNA and protein membrane transporters

Motor domains in DNA and protein transport across biological membranes

Molecular Motors Group - Elena Cabezón and Ignacio Arechaga
. Instituto de Biomedicina y Biotecnología de Cantabria.
Albert Einstein 21, PCTAN 39011 Santander (Spain). Tel. +34 942 202033 | Stats | Analytics