Plasmodium falciparum infected erythrocytes display membrane knobs that are essential for their adherence to vascular endothelia and for prevention of clearance by the spleen. The knob associated histidine rich protein (KAHRP) is indispensable to knob formation and has been implicated in the recruitment and tethering of P. falciparum erythrocyte membrane protein–1 (PfEMP1) by binding to its cytoplasmic domain termed VARC. However, the precise mechanism of interaction between KAHRP and VARC is not very well understood. Here we report that both the proteins co-localize to membrane knobs of P. falciparum infected erythrocytes and have identified four positively charged linear sequence motifs of high intrinsic mobility on KAHRP that interact electrostatically with VARC in solution to form a fuzzy complex. The current study provides molecular insight into interaction between KAHRP and VARC in solution that takes place at membrane knobs.

Application of Non Uniform Sampling (NUS) along with Band-selective Excitation Short-Transient (BEST) NMR experiments has been demonstrated for obtaining the important residue-specific atomic level backbone chemical shift values in short durations of time. This application has been demonstrated with both well-folded (ubiquitin) and unfolded (α-synuclein) proteins alike. With this strategy, the experiments required for determining backbone chemical shifts can be performed very rapidly, i.e., in ∼2 hours of spectrometer time, and this data can be used to calculate the backbone folds of proteins using well established algorithms. This will be of great value for structural proteomic investigations on one hand, where the speed of structure determination is a limiting factor and for application in the study of slow kinetic processes involving proteins, such as fibrillization, on the other hand.