Abstract
The circumsporozoite protein (CSP) forms a dense coat on the surface of the sporozoite, the infective stage of the malaria parasite. The central repeat region of CSP is a critical component of the only licensed malaria vaccine yet little is known about its structure or function. We found that sporozoite mutants with severely truncated or scrambled repeats have impaired motility due to altered adhesion site formation and dynamics, suggesting that the CSP repeats provide a cohesive environment in which adhesion sites can form. We hypothesized that biophysical properties of the repeats are important in this role and interrogated this using single-molecule fluorescence-force spectroscopy. We show that the repeats are a stiff, linear spring with elastic properties, dependent upon length and lost when the repeats are scrambled. These data are the first evidence that the CSP repeat region serves a functional role during infection and motility, likely mediated through its biophysical properties.
Summary No clear function of the central repeat region of the malaria circumsporozoite protein has been described to date, despite its central role in the only licensed malaria vaccine. Here we use mutational analysis and single-molecule fluorescence-force spectroscopy to describe the structural properties and determine the function of this conserved region and important vaccine target.
Highlights The CSP repeats have properties of a linear spring
Scrambling or large truncations of the repeats leads to defects in sporozoite motility
Motility defects are attributed to abnormal formation of adhesion sites
Competing Interest Statement
The authors have declared no competing interest.
