Researchers at IRB Barcelona have succeeded in following the correlated movements of ubiquitin’s amino acids located far away from one another to transfer information across protein structures.
Proteins are the main perpetrators of almost all vital body functions. Cells grow and differentiate in response to the activities of the particular set of proteins expressed at a given time in different cell types. In order to fulfil their complex tasks, proteins interact physically with others in coordinated and precise ways. These interactions are a way by which proteins communicate, the beating heart of almost all intracellular and extracellular processes. In spite of the importance of protein-protein interactions, very little is known about how information flows across protein structures after binding to produce a response.
Through a successful combination of NMR experiments and computational modelling, scientists led by ICREA researcher Xavier Salvatella, with the Joint Programme on Computational Biology between IRB Barcelona and the Barcelona Supercomputing Centre, and Professor Christian Griesinger at the Max Planck Institute for Biophysical Chemistry, have followed the movements of the 76 amino acids of the model protein ubiquitin. The study, published in the Journal of the American Chemical Society (JACS), demonstrates the existence of weak long-range motions correlated between distal residues within the protein-binding interface. “That the atoms of the surface of ubiquitin move in a correlated fashion can make protein-protein interactions more efficient”, explains Salvatella. “The process of information transfer along the structure of the protein is fascinating and its understanding can have many applications in drug discovery”.
Ubiquitin, as the name suggests, is a highly ubiquitous small protein found in almost all tissues of all eukaryotic organisms. Among other functions, it directs unnecessary or damaged proteins for degradation. For this, ubiquitin interacts covalently with many different proteins, thus making ubiquitin an ideal model system for studying protein-protein interaction and dynamics.
Using sophisticated computational and experimental methods Salvatella and collaborators have shown that at least four of the five beta-strands of the protein move in a finely tuned choreography. “The ubiquitin beta-strands form a long communication channel throughout the protein. The correlated motions of amino acids separated by up to 15Å, the equivalent of half the size of a standard protein, allows the information to flow”, continues Salvatella. “These long-range correlated motions among distal parts of the protein, linked by non-covalent interactions, might have implications for molecular recognition because they can promote that all atoms involved in protein binding move in a concerted way.”
Weak Long-Range Correlated Motions in a Surface Patch of Ubiquitin Involved in Molecular Recognition.
Fenwick RB, Esteban-Martín S, Richter B, Lee D, Walter KF, Milovanovic D, Becker S, Lakomek NA, Griesinger C, Salvatella X.
JACS (2011) [doi: 10.1021/ja200461n]