Biophysical characterization of the Plasmodium falciparum circumsporozoite protein's N-terminal domain.

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 P. 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 (IDR) displaying some degree of compaction. This article is protected by copyright. All rights reserved.