Dynamic association of PfEMP1 and KAHRP in knobs mediates cytoadherence during Plasmodium invasion.
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.
International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, India - 110 067.
Akshay Kumar
AK
Ganguly
Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT), Bombay, Mumbai, India - 400 076.
Priyatosh
P
Ranjan
Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT), Bombay, Mumbai, India - 400 076.
Ashutosh
A
Kumar
International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, India - 110 067.
Neel Sarovar
NS
Bhavesh
D020816:Amino Acid Motifs; D002448:Cell Adhesion; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005455:Fluorescent Antibody Technique; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D012996:Solutions
D064267:Intrinsically Disordered Proteins; D010455:Peptides; D015800:Protozoan Proteins; D012996:Solutions; C042968:knob protein, Plasmodium falciparum