Molecular chaperon: how to avoid adhesive situations
Around twenty families of proteins meet the requirements to act as molecular chaperons: to help the proper folding of several polypeptide chains, contributing to the availability of a stable and active in vivo conformation. Txaperones, facing the sequence, have nothing to do with proteins that help bend and have no interaction with them after proteins have taken their original three-dimensional structure. At least seven families are synthesized fairly in stressful situations (both thermal and chemical).
Acting or not as txaperon depends on its ability to recognize and unify the hydrophobic regions of proteins that extend to the intracellular medium. These proteins begin to work in the synthesis and folding of polypeptide chains or in the loss of the original structure caused by any type of environmental stress. It prevents the reversible and non-covalent link between protein and txaperon, as well as the intermolecular interactions between hydrophobic (adhesive) regions subjected to solvent (irreversible aggregation) or early polypeptide chain proteolysis.
Although these proteins play an important biological role, we do not know precisely their mechanism of action. The crystalline structure of several chaperones has allowed to investigate through directional mutagenesis and postulate the supposed mechanism of action. The best known of the systems is the GroE, formed by a Txaperonina, the Groel and its corresponding partner of txaperonina, Groes. The groel is a tetradecarmer with two rings formed by two equal subunits. In the cavity of each ring is the protein substrate to be folded, which prevents interactions with other proteins and therefore possible aggregations.
The coarse is a heptameric protein that diarrhea as a blanket of the "pot" or cavity of the GRoel and that allows its elimination to the protein substrate in suitable conditions so that by itself try to obtain an original structure. These proteins, in a unitary way and with an energy expenditure (by hydrolysis of ATP by Groel), allow obtaining the appropriate folding of numerous polypeptide sequences. From the functional point of view, it should be noted that the oligomeric structure of the Groel allows communication between subunits of the same and different ring to optimize the activity of the system.
The questions that we want to answer through the project and that will help us understand its mechanism of action are:
- In the conformations that polypeptide chains can have along their folding, who has stable interactions with txaperonin?
- How do the biological functions of txaperones influence the union changes produced by different bonds (nucleotides, substrates...)?
- Is txaperonin capable of folding and oligomerizing without the help of other proteins? In other words, what helps txaperonin when it is folded, in physiological and stress conditions?
- Project title: Relationship between structure and function in type I chaperonins (DGICYT PB97-1225).
- Objective: Analysis of the structural bases of the txaperonaria activity.
- Director: Free announcement
- Research team: Asier Galan,Aitor Hierro, Adelina Prado,Begoña Sot and Maria Angeles Urbaneja
- Department: Biochemistry and Molecular Biology
- Centre: Faculty of Science
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