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.
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.
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.