The Cysteine-Rich Interdomain Region from the Highly Variable Plasmodium falciparum Erythrocyte Membrane Protein-1 Exhibits a Conserved Structure
Figure 7
Sequence comparison of MC179, CIDR, and DBL domains.
(A) Alignment of four CIDR and four DBL domains with the lines numbered 1–8 for clarity of discussion. Lines 1–4 show MC179 and the MC179-like portions of three other CIDR domains: line 1, CIDR1α MC179; line 2, CIDR1α of A4var PfEMP1; line 3, CIDR1α of PF10_0001 of 3D7; and line 4, CIDR2γ of the MC strain (see [B]). Lines 5–8 show four DBL domains: line 5, Pkα; line 6, EBA-F1; line 7, EBA-F2; and line 8, DBL1α of MC PfEMP1. The sequence alignment is based on conserved cysteines (green), conserved hydrophobic residues (boxed), and on superimposed X-ray structures. Note the differing lengths and high sequence diversity in regions of lines 2–8 that are aligned with the a, b, and c helices (yellow) that connect H2 and H3 of MC179. The short connection between the H2 and H3 helices in the non-PfEMP1 DBL domains (lines 5–7) contrasts with the much longer connection observed in the MC179 structure (line 1), predicted in other CIDR domains (lines 2–4), and predicted in DBL1α (line 8). Note the long loop in DBL1α that connects the H1 and H2 helices. The end of the H2 helix is marked (red dot). Helices from the MC179 structure are positioned over the MC179 sequence in line 1. MC179 is numbered 1–179 based on the PDB accession code 3C64, which is the same sequence as residues 576–754 of GenBank U27338. The other sequences are numbered as in their GenBank or PDB depositions with accession codes: A4var, L42244; PF10_0001; CIDR2 MC, U27338; Pkα, 2C6L; EBA-F1, 1ZRO; EBA-F2, 1ZRO; DBL1α MC, U27338. (B) Diagram of the entire PfEMP1 from the MC strain showing the alternating DBL and CIDR domains as in Figure 1. Filled boxes denote locations of the “DBL1α MC,” “CIDR1 MC179,” and “CIDR2 MC” sequences that are aligned in (A).