Biophysical characterization of the <i>Plasmodium falciparum</i> circumsporozoite protein's N‐terminal domain
Rob Geens, Jessica J. Stanisich, Olivier Beyens, Stijn D'Hondt, Jean‐Michel Thiberge, Amber Ryckebosch, Anke de Groot, Stefan Magez, Didier Vertommen, Rogério Amino, Hans De Winter, Alexander N. Volkov, Péter Tompa, Yann G.‐J. Sterckx
Abstract
Abstract The circumsporozoite protein (CSP) is the main surface antigen of the Plasmodium sporozoite (SPZ) and forms the basis of the currently only licensed anti‐malarial vaccine (RTS,S/AS01). CSP uniformly coats the SPZ and plays a pivotal role in its immunobiology, in both the insect and the vertebrate hosts. Although CSP's N‐terminal domain (CSP N ) has been reported to play an important role in multiple CSP functions, a thorough biophysical and structural characterization of CSP N is currently lacking. Here, we present an alternative method for the recombinant production and purification of CSP N from Plasmodium falciparum (PfCSP N ), which provides pure, high‐quality protein preparations with high yields. Through an interdisciplinary approach combining in‐solution experimental methods and in silico analyses, we provide strong evidence that PfCSP N is an intrinsically disordered region displaying some degree of compaction.