PfEMP1, SURFIN/PvSTP1, SICAvar and two P. falciparum DBL-containing proteins are interrelated through the modular and structurally conserved intracellular tryptophan-rich domain (WRD). (A) Intracellular regions (right of aligned black transmembrane domains) of SURFIN, PvSTP1, SICAvar, PfEMP1, and two DBL-containing proteins carry 1–7 copies of WRDs (dashed rectangles), which themselves are composed of a variable number of conserved WRD-A (green) and WRD-B (blue) subdomains. Note conservation of complete WRDs (consisting of one A and two B subdomains) in P. knowlesi SICAvar-like gene PKH_081360 and in the bird parasite P. gallinaceum (PgSurf1 and PgSurf2). A dashed rectangle extending beyond subdomains indicates that the WRD but not all its subdomains reached statistical significance (E ≤ 0.01) in the Hmmer search. (B) Multiple sequence alignment of selected sequences representing the WRD-A (top) and WRD-B (bottom) subdomains. “/1” and “/2” after protein IDs denote first and second occurrences of a subdomain within a (not necessarily the same) WRD, respectively. Darker shades of gray indicate higher conservation. (C) Tertiary structure of PfEMP1 intracellular domain (ATS) as recently determined using NMR spectroscopy (Mayer et al., 2012). The structure reveals a conserved core composed of four alpha helices, which map to the conserved sequence blocks of the WRD-A and WRD-B subdomains as indicated by red bars above alignments. Abbreviations: LCR… low complexity region.