title: Effects of environmental factors on MSP21-25 aggregation indicate the roles of hydrophobic and electrostatic interactions in the aggregation process.
abstract: Merozoite surface protein 2 (MSP2), one of the most abundant proteins on the merozoite surface of Plasmodium falciparum, is recognized to be important for the parasite's invasion into the host cell and is thus a promising malaria vaccine candidate. However, mediated mainly by its conserved N-terminal 25 residues (MSP21-25), MSP2 readily forms amyloid fibril-like aggregates under physiological conditions in vitro, which impairs its potential as a vaccine component. In addition, there is evidence that MSP2 exists in aggregated forms on the merozoite surface in vivo. To elucidate the aggregation mechanism of MSP21-25 and thereby understand the behavior of MSP2 in vivo and find ways to avoid the aggregation of relevant vaccine in vitro, we investigated the effects of agitation, pH, salts, 1-anilinonaphthalene-8-sulfonic acid (ANS), trimethylamine N-oxide dihydrate (TMAO), urea, and sub-micellar sodium dodecyl sulfate (SDS) on the aggregation kinetics of MSP21-25 using thioflavin T (ThT) fluorescence. The results showed that MSP21-25 aggregation was accelerated by agitation, while repressed by acidic pHs. The salts promoted the aggregation in an anion nature-dependent pattern. Hydrophobic surface-binding agent ANS and detergent urea repressed MSP21-25 aggregation, in contrast to hydrophobic interaction strengthener TMAO, which enhanced the aggregation. Notably, sub-micellar SDS, contrary to its micellar form, promoted MSP21-25 aggregation significantly. Our data indicated that hydrophobic interactions are the predominant driving force of the nucleation of MSP21-25 aggregation, while the elongation is controlled mainly by electrostatic interactions. A kinetic model of MSP21-25 aggregation and its implication were also discussed.
authors.affiliation: School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, 230601, Anhui, People's Republic of China, turenzh@ahu.edu.cn.
authors.forename: Xuecheng
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuanqiu
authors.initials: Y
authors.lastname: Dong
authors.forename: Jigang
authors.initials: J
authors.lastname: Yu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Tu
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D000953:Antigens, Protozoan / Q000737:chemistry*; D052160:Benzothiazoles; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008744:Methylamines / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D055503:Protein Multimerization; D015800:Protozoan Proteins / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D055672:Static Electricity; D013844:Thiazoles / Q000737:chemistry; D014508:Urea / Q000737:chemistry
chemical_list: D000817:Anilino Naphthalenesulfonates; D000953:Antigens, Protozoan; D052160:Benzothiazoles; D008744:Methylamines; D010446:Peptide Fragments; D015800:Protozoan Proteins; D013844:Thiazoles; C065974:merozoite surface protein 2, Plasmodium; C009462:thioflavin T; D012967:Sodium Dodecyl Sulfate; C027132:1-anilino-8-naphthalenesulfonate; D014508:Urea; C005855:trimethyloxamine