Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs
Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen‐like proteins (SmVALs) from the SCP/TAPS (sperm‐coating protein/Tpx/antigen 5/pathogenesis related‐1/Sc7) superfamily. The first SmVAL st...
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Published in | Acta crystallographica. Section D, Biological crystallography. Vol. 70; no. 8; pp. 2186 - 2196 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
5 Abbey Square, Chester, Cheshire CH1 2HU, England
International Union of Crystallography
01.08.2014
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen‐like proteins (SmVALs) from the SCP/TAPS (sperm‐coating protein/Tpx/antigen 5/pathogenesis related‐1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C‐terminal extension. SmVAL4 has the characteristic α/β‐sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino‐acid residues and is missing the histidines that coordinate divalent cations such as Zn2+ in other SCP/TAPS proteins. SmVAL4 has a cavity between α‐helices 1 and 4 that was observed to bind lipids in tablysin‐15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol‐export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid‐binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1. |
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Bibliography: | ArticleID:AYD2BE5268 istex:8827B69E53180E53E3B9BB3EE46C0270F6125BE9 ark:/67375/WNG-3F7BGMWM-W ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to the work. |
ISSN: | 1399-0047 0907-4449 1399-0047 |
DOI: | 10.1107/S1399004714013315 |