Title
Biochemical, biophysical and molecular dynamics studies on the proteoglycan-like domain of carbonic anhydrase IX
Author
Emma Langella, Martina Buonanno, Daniela Vullo, Nina Dathan, Marilisa Leone, Claudiu T. Supuran, Giuseppina De Simone, Simona Maria Monti
Year
2018
Journal
Cellular and Molecular Life Sciences
Abstract
Human carbonic anhydrase IX (hCA IX) is a tumour-associated enzyme present in a limited number of normal tissues, but overexpressed in several malignant human tumours. It is a transmembrane protein, where the extracellular region consists of a greatly investigated catalytic CA domain and a much less investigated proteoglycan-like (PG) domain. Considering its important role in tumour biology, here, we report for the first time the full characterization of the PG domain, providing insights into its structural and functional features. In particular, this domain has been produced at high yields in bacterial cells and characterized by means of biochemical, biophysical and molecular dynamics studies. Results show that it belongs to the family of intrinsically disordered proteins, being globally unfolded with only some local residual polyproline II secondary structure. The observed conformational flexibility may have several important roles in tumour progression, facilitating interactions of hCA IX with partner proteins assisting tumour spreading and progression.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Thermal stability, Chemical stability, Protein folding, Protein denaturation, Biochemistry