Viruses and bacteria utilize proteins to attach and infect cells and tissues. Viruses have envoloped proteins that especifically recongnize receptors in the surface of the target cells. HIV-1 recognices receptor CD4 in the surface of T cell throghout its envolope glycoprotein gp120. In the case of bacteria, they attach to tissues using long filament called pilus. Bacterial pilus type 1 is composed of several protein subunit arranged in chain, FimA-FimG-FimG-FimH. The more external domain, FimH, is the adhesin binding domain that establishes the mechanical anchoring to tissues. Both, bacterial and viral proteins withstand mechanical forces than can go from few piconewtons to hundreds. However, very little is known about how force modify the structure and features of these proteins and ultimately how its affects infection. In this project we aim to investigate the effect of mechanical forces in the anchoring proteins and its role during attachment. We will concentrate in viral receptors CD4 and bacterial fimbriae proteins (Fim). We will use a novel atomic force spectometer that allows us to apply calibrated forces to a single protein molecule. This technique allows also monitoring chemical reaction under force such as the reduction of disulfide bonds or the binding of peptides and antibodies. These processes are known to be implicated in the infection of viruses and bacteria and they may have a mechanical origin. We will use bioinformatics and high-throughout screening techniques to identify molecules that alter the nanomecanichs of these anchoring proteins and that can potentially be used to prevent infections.
Fields of science
Call for proposal
See other projects for this call