The pathogenicity of Plasmodium falciparum is caused by electron-dense knob-like structures on the surface of malaria-infected erythrocytes that sequester malaria-infected erythrocytes in the vascular endothelium. Knob-associated Histidine-rich protein (KAHRP), a member of exported malaria proteins, contributes to the knob formation in infected erythrocytes. It interacts with erythrocytes skeletal proteins such as spectrin, actin and ankyrin and Plasmodium falciparum erythrocyte membrane protein (PfEMP1).

The unique spiral shaped morphology of knobs isolated from malaria-infected erythrocytes observed by transmission electron microscopy (TEM) is caused by self-assembling between histidine-rich amino terminal segment and a lysine-rich segment located within the carboxyl half of KAHRP. This process was simulated by using GST (glutathione S-transferase) fusion histidine-rich N-terminus and Trx (thioredoxin) fusion lysine-rich C-terminus peptides of the entire length of KAHRP to obtain the associated structures.

Under TEM, the structures display tight binding and form spiral-like or circle-like structures and their sizes range from 100-120 nm, which are close to the protrusions observed at mature asexual stages (trophozoites and schizonts) obtained by using Scanning Electron Microscopy (SEM) and atomic force microscopy (AFM).

The structure imaging through TEM, SEM and AFM offers a qualitative and quantitative means of visualizing the sub-micron details of knob formation with implications in the design of new antimalarial strategies.