José M. Casasnovas
Group Leader
Research summary
Our group researches on receptor-ligand recognition using biochemical techniques and X-ray crystallography, studying receptors of the immune system, some of which have been subverted by viruses to enter into host cells.
Publications
Santiago C, Mudgal G, Reguera J, Recacha R, Albrecht S, Enjuanes L, Casasnovas JM. Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection. Scientific Reports 2017; 7, 46045, doi: 10.1038/srep46045.
Echbarthi M, Zonca M, Mellwig R, Schwab Y, Kaplan G, DeKruyff RH, Roda‐Navarro P, Casasnovas JM. Distinct trafficking of cell surface and endosomal TIM-1 to the immune synapse. Traffic 2015, 16, 1193-1207, doi: 10.1111/tra.12329
Angiari S, Donnarumma T, Rossi B, Dusi S, Pietronigro E, Zenaro E, Della Bianca V, Toffali L, Piacentino G, Budui S, Rennert P, Xiao S, Laudanna C, Casasnovas JM, Kuchroo V, Constantin G. TIM-1 Glycoprotein Binds the Adhesion Receptor P-Selectin and Mediates T Cell Trafficking during Inflammation and Autoimmunity. Immunity 2014; 40:542-553
Recacha R, Jiménez D, Tian L, Barredo R, Gahmberg CG, Casasnovas JM. Crystal structures of an ICAM-5 ectodomain fragment show electrostatic-based homophilic adhesions. Acta Cryst 2014; D70:1934-1943
Reguera J, Mudgal G, Santiago C, Casasnovas JM. A structural view of coronavirus-receptor interactions. Virus Res 2014; 194:3-15
Our group studies the cell surface molecules that regulate the immune system and virus entry into host cells. We analyse receptor-ligand interactions related to immune processes such as cell adhesion and phagocytosis, as well as virus binding to cells. In addition, we characterise virus neutralization by humoral immune responses and its correlation with virus entry into cells. Our research has provided key observations regarding immune receptor function, and has identified viral epitopes essential for virus infection, some of which are targeted by neutralizing antibodies. Our multidisciplinary research applies structural (X-ray crystallography), biochemical and cell biology approaches.
Cell-cell interactions
We studied how members of the TIM domain (T cell/transmembrane, immunoglobulin and mucin domain) and ICAM (intercellular cell adhesion molecules) subfamilies mediate cell-cell interactions. The TIM proteins are pattern recognition receptors, specialised in recognition of the PtdSer (phosphatidylserine) cell death signal. We helped to show that TIM-1 mediates the cell adhesion interaction that regulates T cell trafficking during inflammation. The ICAM proteins have long been linked to cell adhesion processes. Our recent research focused on ICAM-5, a protein expressed exclusively in telencephalic neurons. We used X-ray crystallography to determine how ICAM-5 mediate cell adhesion among neurons. ICAM-5 has an S-shaped configuration that supports formation of a cell adhesion complex built of multiple molecules on the neuron surface.
Virus-receptor interactions and virus neutralisation by antibodies
To analyse virus-receptor interactions in measles virus and coronavirus, we determined crystal structures of virus-receptor complexes. These structures defined the way in which measles virus and certain coronavirus bind to cell surface proteins; we identified the principal determinants of receptor recognition in those viruses. Moreover, we are analysing how antibodies prevent and neutralise virus infections. Potent neutralising antibodies of measles virus and coronavirus target virus residues engaged in binding to cell surface receptors, indicating that prevention of virus entry into host cells is a major mechanism of virus neutralisation by the immune system.
