Three-dimensional solution structure of the extracellular region of the complement regulatory protein CD59, a new cell-surface protein domain related to snake venom neurotoxins

Kieffer B, Driscoll PC, Campbell ID, Willis AC, van der Merwe PA, Davis SJ. (1994), Biochemistry. 33, 4471-82

Abstract

The cell surface antigen CD59 is an inhibitor of complement-mediated lysis and a member of the Ly6 superfamily (Ly6SF) of cysteine-rich cell-surface molecules whose sequences are related to those of snake venom neurotoxins. The three-dimensional solution structure of a recombinant form of the extracellular region of the molecule (residues 1-70 of the mature protein; sCD59) has been solved by 2D NMR methods. sCD59 is a relatively flat, disk-shaped molecule consisting of a two-standed beta-sheet finger loosely packed against a protein core formed by a three-stranded beta-sheet and a short helix. Structure calculations allowed an unambiguous assignment of the disulfide-bonded cysteine pairs as 3-26, 6-13, 19-39, 45-63, and 64-69. The topology of sCD59 is similar to that of the snake venom neurotoxins and consistent with an evolutionary relationship existing between the Ly6SF and the neurotoxins.

Key figure

MOLSCRIPT pictures of (A) the restrained minimized average structure (SA)_r of sCD59 and (B) the X-ray crystal structure of N. naja siamensis α-cobratoxin (PDB code 2CTX) showing the secondary structure elements and the positions of the disulfide bond connections. The structures are shown in the same orientation to emphasize the similarity of the overall topology, disulfide pattern, and core secondary structure; the orientation of sCD59 is similar to that in Figure 6A and Figure 7 (left). The side chains of the disulfide-bonded cysteine residues and the glycosylated Asn-18 residue of sCD59 are shown in “ball and stick” form.