hyp

hyp. 2]. A number of these proteins have been recognized [3]. MSP-1, 2, 4, 5, 8, and 10 proteins are linked to the membrane of the parasite via a glycosylphosphatidylinositol (GPI) membrane anchor [4C6]. These proteins, except MSP-2, have one DM1-Sme or two epidermal growth element (EGF)-like domains in the carboxyl terminus. Additional MSPs such as MSP3, MSP6, MSP-7 and MSP-9 are soluble, hydrophilic and are, in part, associated with the merozoite surface [7C11]. DM1-Sme Although many proteins are known to play an important part in merozoite invasion, their three-dimensional structure and specific functions remains unknown. Consequently, a complete understanding of the structural characteristics and molecular relationships that are the basis of the invasion process is critical, not only for improving our knowledge about the basic biology of the malaria parasite, but also for the development of vaccine and the additional intervention strategies to counter the disease. In this work, we focused on MSP3 protein which is a encouraging candidate antigen for anti-malaria vaccines [2, 12, 13]. Earlier studies suggested that MSP3 protein is located within the merozoite surface but does not contain a transmembrane website or GPI anchor consensus sequence and so presumably is definitely attached to the merozoite surface as a result of protein-protein relationships [9, 13, 14]. MSP3 offers sequence similarity within the 1st ~50 residues that contain putative transmission peptide with several other surface malaria proteins (Fig. 1). The precursor form of MSP3 may undergo cleavage in its N-terminal region during schizogony to generate a mature processed form [15]. The central regions of MSP3 and the Mouse monoclonal to IKBKB additional homologous proteins are different. MSP3 consists of three blocks of alanine-rich heptad repeats that are expected to form an intramolecular coiled coil structure [11], while, for example, MSP6 has an aperiodic hydrophilic sequence. In the next region toward the C-terminus, some proteins, including MSP3, share a motif (ILGWEFGGG-[AV]-P) followed by an acidic region. Finally, they show a C-terminal ~40 residue website with the highest degree of sequence similarity [9]. The sequence analysis of this C-terminal website yielded ambiguous conclusions; in the beginning, it was suggested that this C-terminal region consists of a leucine-zipper like motif [14]. However, additional authors did not identify this motif in either MSP3 or MSP6 and expected that MSP6 offers two amphipathic -helices separated by a loop therefore forming intramolecular contacts with each other [9]. Earlier biophysical study of the full size MSP3 and four smaller peptides [16] suggested that all tested samples have a large portion of Chelical and random coil conformations. The cross-linking and analytical ultracentrifugation experiments suggested that the full size MSP3 forms elongated dimers and tetramers. The study also proposed a crucial role of the last 55 C-terminal residues in oligomerization of MSP3. Open in a separate window Number 1 A family of malaria surface proteins comprising common C-terminal website(a) A schematic diagram of the website organization of proteins that contain a common C-terminal coiled coil website. (b) Sequence positioning of the C-terminal website of malaria proteins. Bold uppercase characters of the consensus show conserved apolar residues. The top part of the alignment consists of proteins: GLURP, glutamate rich protein (PF10_0344), MSP3 (PF10_0345), MSP6 (PF10_0346), H101(PF10_0347), MSPDBL1 (PF10_0348), M712 (PF10_0350), M566 (PF10_0351), MSP11 (PF10_0352), MSPDBL2 (PF10_0355), LSA-1, liver stage antigen-1 (PF10_356). The lower part of the positioning consists of Sal-1 proteins: putative MSP3 (PV110965), putative MSP (PV097690), putative MSP3a (PV097695). hyp. proteins PC104352 and PC101322. latency connected antigen (PY01017). hyp. protein PB105994. The conserved 40-residue region of the alignment with the (abcdefg)n heptad repeats is definitely underlined and their a and d positions are demonstrated. In the present study, by applying bioinformatics approaches, we have extended the list of proteins having the MSP3-like C-terminal website from 4 to 10 in and 7 in the additional varieties of proteins MSP3, MSP6, MSP11 (or H103) and H101 have a similar N-terminal apolar region resembling the transmission sequence followed by a common motif with the NLRng consensus sequence (Fig. 1) [9, 26]. The central regions of these proteins are different, while at their C-terminal region they again share a motif having a consensus sequence gwEfgGGap followed by an acidic region and an Chelical coiled coil region [26]. We were particularly interested in the C-terminal ~40 residue region that has the greatest degree of sequence similarity among these proteins and only may DM1-Sme self-assemble into a functional structure..