Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Nov 12;5(4):885-908.
doi: 10.3390/insects5040885.

Evolution and Structural Analyses of Glossina morsitans (Diptera; Glossinidae) Tetraspanins

Edwin K Murungi  1 , Henry M Kariithi  2   3 , Vincent Adunga  4 , Meshack Obonyo  5 , Alan Christoffels  6
Affiliations

Evolution and Structural Analyses of Glossina morsitans (Diptera; Glossinidae) Tetraspanins

Edwin K Murungi et al. Insects. .

Abstract

Tetraspanins are important conserved integral membrane proteins expressed in many organisms. Although there is limited knowledge about the full repertoire, evolution and structural characteristics of individual members in various organisms, data obtained so far show that tetraspanins play major roles in membrane biology, visual processing, memory, olfactory signal processing, and mechanosensory antennal inputs. Thus, these proteins are potential targets for control of insect pests. Here, we report that the genome of the tsetse fly, Glossina morsitans (Diptera: Glossinidae) encodes at least seventeen tetraspanins (GmTsps), all containing the signature features found in the tetraspanin superfamily members. Whereas six of the GmTsps have been previously reported, eleven could be classified as novel because their amino acid sequences do not map to characterized tetraspanins in the available protein data bases. We present a model of the GmTsps by using GmTsp42Ed, whose presence and expression has been recently detected by transcriptomics and proteomics analyses of G. morsitans. Phylogenetically, the identified GmTsps segregate into three major clusters. Structurally, the GmTsps are largely similar to vertebrate tetraspanins. In view of the exploitation of tetraspanins by organisms for survival, these proteins could be targeted using specific antibodies, recombinant large extracellular loop (LEL) domains, small-molecule mimetics and siRNAs as potential novel and efficacious putative targets to combat African trypanosomiasis by killing the tsetse fly vector.

Keywords: CD63; Glossina morsitans; GmTsp; LEL; Trypanosoma; modeling; phylogenetics; positive selection; tetraspanins.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Domain architecture of Glossina morsitans putative tetraspanins. Predicted domain structures of the seventeen G. morsitans are indicated. Transmembrane and large extracellular domain (LEL) domains are depicted as blue round circles and magenta rectangular blocks, respectively. The numbers in the parentheses indicate the coordinates (amino acid residues) of the LEL For details of the coordinates of the TMs, compare this figure with data presented in Table 1 and in Figure A1. N-t and C-t represents the N- and C-termini of the GmTsp proteins, respectively.
Figure 2
Figure 2
Alignment of the G. morsitans GmTsps: The shared secondary structural of the tetraspanins (TM 1–4; SEL, and LEL), the conserved CCG, PxxCC motif (boxed) and the terminal region rich in charged/polar amino acids are shown.
Figure 3
Figure 3
Phylogenetic analysis of tetraspanin homologs based on amino acid sequences: The phylogenetic tree shows clustering of the Tsps into three main clades and nine sub-clades, which display 1:1:1 orthologous relationships of these proteins. The phylogenetic tree was constructed using the ML method implemented in PhyML [81] using the LG model of amino acid substitution [54]. The seventeen putative tsetse fly (G. morsitans) tetraspanins identified in this study (see Table 1) were phylogenetically compared to homologs in the fruit fly (D. melanogaster) and housefly (M. domestica). Nodes with bootstrap support values >80% are marked with solid circles. Gm, Glossina morsitans; Dm, Drosophila melanogaster; Md, Musca domestica. Note: for the abbreviation of the Tsps in this figure, all letters are in upper case; the letters written in lower case in the main text are shown here in decreased font size.
Figure 4
Figure 4
Cartoon representation of the modeled GmTsp42Ed structure: (A) 3-D representation of GmTsp42Ed model, in which the N- and the C-termini are shown as NH2 and COOH, respectively. The four transmembrane domains are color-coded as red, purple, orange and yellow for TM1 to TM4, respectively. The LEL domain which is located between TM3 and TM4 has three α-helices and two anti-parallel β-strands and is shown in cyan; (B,C) 2-D representation of the orientation of the cytoplasmic (shown in blue), non-cytoplasmic (small extracellular loop (SEL) and LEL domains) (shown in green), and TM1-4 helices (shown in yellow) of G. morsitans GmTsp42Ed and the human tetraspanin (HsTspCD63), respectively. The alignments of GmTsp42Ed and HsTspCD63 are shown at the bottom of the domain orientations. The dotted lines in Panels (B) and (C) represent a hypothetical cellular plasma membrane.
Figure 5
Figure 5
Ramachandran plots for GmTsp42Ed: The plot statistics are indicated for all the non-glycine and non-proline residues that fell within the favored regions. Shown in red, yellow, pale yellow, and white, respectively, are amino acid residues in most favored, additionally allowed, generously allowed, and disallowed regions. Based on the analysis of 118 structures of resolution of at least 2.0 Angstroms and R-factor no greater that 20%, a good model is expected to have ≥90% in the most favored regions. The plots were generated using PROCHECK v. 3.5.4 [66].
Figure A1
Figure A1
Distribution of the structural features of seventeen G. morsitans putative tetraspanins detected in this study: The start and end of the domains/motifs are indicated by the coordinates of the amino acid residues (shown with black numbers with vertical bars). The palmitoylation sites are shown in blue bold letters; the transmembrane domains(TM1–4) are depicted in light blue; the SEL motifs are in pink; the CCG domains are shown in red; the LEL motifs are shown in light green, while the PxxCC motifs are in dark blue. Notice that six of the GmTsps do not contain the PxxCC motif.
Figure A1
Figure A1
Distribution of the structural features of seventeen G. morsitans putative tetraspanins detected in this study: The start and end of the domains/motifs are indicated by the coordinates of the amino acid residues (shown with black numbers with vertical bars). The palmitoylation sites are shown in blue bold letters; the transmembrane domains(TM1–4) are depicted in light blue; the SEL motifs are in pink; the CCG domains are shown in red; the LEL motifs are shown in light green, while the PxxCC motifs are in dark blue. Notice that six of the GmTsps do not contain the PxxCC motif.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Maudlin I. Transmission of African trypanosomiasis: Interactions among tsetse immune system, symbionts, and parasites. In: Harris K., editor. Advances in Disease Vector Research. 7th ed. Springer; New York, NY, USA: 1991. pp. 117–148.
    1. Vreysen M.J.B. Prospects for area-wide integrated control of tsetse flies (Diptera: Glossinidae) and trypanosomosis in sub-Saharan Africa. Rev. Soc. Entomol. Argent. 2006;65:1–21.
    1. Brun R., Blum J., Chappuis F., Burri C. Human African trypanosomiasis. Lancet. 2010;375:148–159. doi: 10.1016/S0140-6736(09)60829-1. - DOI - PubMed
    1. Chappuis F., Loutan L., Simarro P., Lejon V., Büscher P. Options for field diagnosis of human African trypanosomiasis. Clin. Microbiol. Rev. 2005;18:133–146. doi: 10.1128/CMR.18.1.133-146.2005. - DOI - PMC - PubMed
    1. Burri C., Nkunku S., Merolle A., Smith T., Blum J., Brun R. Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: A randomised trial. Lancet. 2000;355:1419–1425. doi: 10.1016/S0140-6736(00)02141-3. - DOI - PubMed

LinkOut - more resources