# The Plasmodium CSP repeats have elastic properties with a critical role in sporozoite motility

## TL;DR

This study shows that the Plasmodium CSP protein's repeat region has elastic properties that are crucial for the parasite's movement by enabling proper adhesion site formation.

## Contribution

The study reveals a novel functional role of CSP repeats in sporozoite motility through their elastic properties.

## Key findings

- CSP repeats behave like a stiff, linear spring with elastic properties dependent on their length.
- Truncated or scrambled CSP repeats impair sporozoite motility due to altered adhesion site dynamics.
- CSP repeats are essential for the formation of adhesion sites necessary for gliding motility.

## Abstract

The Plasmodium circumsporozoite protein (CSP) is the major surface protein of the sporozoite, the infective stage of the malaria parasite. The central repeat region of CSP is the primary immunological target of the sporozoite stage, yet little is known about its structure or function. Here, we show that sporozoite mutants with truncated or scrambled CSP repeats exhibit impaired motility due to altered adhesion site formation and dynamics. Since CSP forms the environment in which the thrombospondin-related anonymous protein (TRAP)-containing adhesion sites assemble, our data suggest that the dense CSP coat is altered in the repeat mutants, affecting adhesion site formation. We hypothesized that this role depends on the biophysical properties of the repeats, and used single-molecule fluorescence-force spectroscopy to test this hypothesis. Our results indicate that the CSP repeats behave like a stiff, linear spring with elastic properties that depend on its length and are lost when the repeats are scrambled. These data provide evidence for a functional role of the CSP repeat region during Plasmodium infection and motility.

Although the central repeat region of the Plasmodium circumsporozoite protein (CSP) is the main target of protective antibodies against the parasite, its structure and function are little understood. This study characterizes the biophysical properties of the CSP repeats and demonstrates an important role for the repeats in the parasite’s ability to move within its mosquito and mammalian hosts.

CSP repeat truncation or scrambling impairs sporozoite motility.CSP repeats enable the formation of adhesion sites on the sporozoite’s surface that are necessary for gliding motility.CSP repeats have elastic properties and behave like a stiff, linear spring.

CSP repeat truncation or scrambling impairs sporozoite motility.

CSP repeats enable the formation of adhesion sites on the sporozoite’s surface that are necessary for gliding motility.

CSP repeats have elastic properties and behave like a stiff, linear spring.

The central repeat region of the circumsporozoite protein (CSP) enables the formation and turnover of adhesion sites on the parasite surface.