Decoding the language of var genes and Plasmodium falciparum sequestration

Sequestration and rosetting are key determinants of Plasmodium falciparum p athogenesis. They are mediated by a large family of variant proteins called P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 proteins are multispecific binding receptors that are transported to parasite-induced, 'knob-like' binding structures at the erythrocyte surface. To evade immunit y and extend infections, parasites clonally vary their expressed PfEMP1. Th us, PfEMP1 are functionally selected for binding while immune selection act s to diversity the family. Here,we describe a new way to analyse PfEMP1 seq uence that provides insight into domain function and protein architecture w ith potential implications for malaria disease.