Dr. Andrea Prota

Curriculum Vitae

We use X-Ray crystallography in combination with biochemical and biophysical methods to provide the molecular mechanisms of protein interactions implicated in the regulation of the microtubule cytoskeleton. The elucidation and further exploration of these interactions at atomic resolution are pivotal to both basic and applied research in this field, and have important implications for the treatment of cancer and neurodegenerative diseases.

Our research activities are dedicated to the structural analysis of tubulin interactions with microtubule-targeting agents (MTAs). MTAs like taxol efficiently block cell entry into mitosis and are among the most potent chemotherapeutic drugs used for the treatment of different types of cancers. Despite the importance of MTAs for medical and basic research applications, their molecular mechanisms of action often remain elusive. Using X-ray crystallography and cryo EM we study the mechanisms of action of diverse MTAs by determining their structures in complex with tubulin and microtubules to high resolution.

Our research portfolio further covers the structural analysis of tubulin-complexes with various modulatory proteins. As part of the EU-funded Innovative Training Network TubInTrain https://www.tubintrain.eu, we study the role of microtubules in neurotoxicity and neurodegenerative disorders. In particular, we investigate different strategies for tuning tubulin/MTs dynamics and interactions with selected proteins and ligands at the atomic level, aiming at providing new relevant indications for the future design of effective drugs or novel therapeutic interventions.

2019

Horizon 2020 MSCA-ITN EJD Grant TubInTrain (www.tubintrain.eu).

The TubInTrain network has participants from six European countries and encompasses ten academic groups and ten companies committed to creating an outstanding training program for thirteen early stage researchers (ESRs) to elucidate the mechanisms of neurodegeneration associated to microtubules structure and dynamics.

Prota AE, Sage DR, Stehle T, Fingeroth JD
The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding
Proceedings of the National Academy of Sciences of the United States of America PNAS. 2002; 99: 10641.

Original publication: 10.1073/pnas.162360499

Chappell JD, Prota AE, Dermody TS and Stehle T
Crystal structure of reovirus attachment protein sigma1 reveals evolutionary relationship to adenovirus fiber 
EMBO J 21, 1-11 (2002).

Original publication: 10.1093/emboj/21.1.1

Vogt J, Perozzo R, Pautsch A, Prota A, Schelling P, Pilger B, Folkers G, Scapozza L and Schulz GE
Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by x-ray crystallography 
Proteins 41, 545-553 (2000).

Original publication: 10.1002/1097-0134(20001201)41:4<545::aid-prot110>3.0.co;2-8

Scapozza L, Ballmer P, Johner R, Perozzo R, Pilger B, Pospisil P, Prota A, Schelling P, Spadola L, Wurth C and Folkers G
Extended substrate acceptance of herpes simplex virus type 1 thymidine kinase: A new chance for gene and antiviral therapy 
CHIMIA International Journal for Chemistry 54, 663-668 (2000).

Prota A, Vogt J, Pilger B, Perozzo R, Wurth C, Marquez VE, Russ P, Schulz GE, Folkers G and Scapozza L
Kinetics and crystal structure of the wild-type and the engineered y101f mutant of herpes simplex virus type 1 thymidine kinase interacting with (north)-methanocarba-thymidine 
Biochemistry 39, 9597-9603 (2000).

Original publication: 10.1021/bi000668q

Folkers G, Prota A and Merz A
Modelling of guanine-derivative-protein interaction complexes as a basis of drug design 
Farmaco 50, 449-454 (1995).