Predicted disulfide-bonded structures for three uniquely related proteins of Plasmodium falciparum, Pfs230, Pfs48/45 and Pf12.
Pfs230 is a surface protein of the gametes of Plasmodium falciparum and has been demonstrated to be a target of malaria transmission-blocking antibodies; it is an important candidate antigen for a transmission-blocking vaccine. The target epitopes of transmission-blocking antibodies against Pfs230 are almost all reduction sensitive suggesting that disulfide bonds are critical for folding the native molecule. Following the cloning of the Pfs230 gene attempts are now underway to express subunits of the protein for use in vaccine trials. It will be important to understand the disulfide-bond structure of the Pfs230 to achieve this goal. In this paper we present a model for this structure based on the observation that the Pfs230 molecule contains a series of regularly repeated cysteine-containing motifs. Four such motifs have been identified, together with a fifth cysteineless motif, which occur in the same relative order, with regular alternating omission of specific motifs, 14 times throughout the length of the protein. Each of the 14 sets of motifs contains an even number of cysteine residues (2, 4 or 6). We postulate that each set folds into a separate disulfide-bonded domain in which corresponding pairs of cysteines form an equivalent disulfide bond in every such domain. The postulated bonding arrangements in the different domains are mutually confirmatory throughout the sequence of Pfs230. We have identified two other malaria proteins, Pfs48/45 and Pf12, which share the same arrangements of motifs and conform to the same disulfide-bond structure proposed for Pfs230; no other proteins in the sequence data base share these characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D017780:Malaria Vaccines / Q000302:isolation & purification; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D004220:Disulfides; D017780:Malaria Vaccines; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C084847:pfs48-45 protein, Plasmodium falciparum; D003545:Cysteine