In an article recently published in the prestigious journal Nature Communications, researchers from the Montreal Clinical Research Institute (IRCM) and the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal collaborated with eminent researcher David Barford of the University of Cambridge to shed light on the 3D structure of the ELMO / DOCK2 complex.
The ELMO / DOCK2 complex is an important molecular machine that plays a crucial role in cell migration in the body. Cell migration is fundamental in many ways, including organ formation in the embryo, wound healing, or simply for the delivery of immune system cells to infection sites. However, when deregulated, the ELMO / DOCK complex allows aberrant cell migration and contributes to the formation of metastases, the leading cause of death in people suffering with cancer.
The research resulting from this collaboration helped to unveil the molecular detail underlying the fine-tuning of this “cell movement” machine.
The research team found that the ELMO / DOCK complex is capable of adopting an inactive form in which different regions of proteins fold and fit into each other, much like a Transformers robot. In this “closed” form, regions of ELMO and DOCK2 known to interact with other proteins are masked and therefore inaccessible. In its “open” form - especially when the RAC1 protein, the mediator of cell migration, is engaged - the complex becomes accessible. It then promotes numerous interactions with its target proteins to ensure cell migration.
“This work has generated a large amount of new information about the ELMO / DOCK complex that will stimulate many future studies around the world. This information will also provide a better understanding of the way the entire DOCK family operates,” underlines Jean-François Côté, researcher and Vice-President for Research and Academic Affairs at the IRCM, and Professor in the Department of Medicine at the Faculty of Medicine of Université de Montréal.
“There are 14 ELMO and DOCK proteins, and several are implicated in human diseases. This discovery demystifies some of the fundamental mechanisms responsible for the disease. This is therefore a first step that will certainly lead to a better understanding of metastases and cancer cells,” adds Matthew Smith, Principal Investigator at IRIC and Assistant Professor in the Department of pathology and cell biology at the Faculty of Medicine of Université de Montréal.
Access the full article here.
The Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), the Fonds de recherche du Québec-Santé (FRQS), the Canada Research Chairs (CRC) and the Transat Chair.