6ANY

Structure of BmVAL-1

Summary for 6ANY

• Entry DOI: 10.2210/pdb6any/pdb
• Descriptor: Bm4233, isoform b, alpha-L-fucopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: venom allergen-like, val, ancylostoma secreted protein, asp, sperm coating protein, scp, taps, testis specific proteins, tpx, antigen 5, ag5, pathogenesis related-1, pr-1, sc7, cap, cysteine-rich secretory protein, crisp, venom antigen 5, excretory-secretory products, sterol binding, lipid transport
• Biological source: Brugia malayi (Filarial nematode worm)
• Total number of polymer chains: 1
• Total formula weight: 24526.81

Authors

Asojo, O.A. (deposition date: 2017-08-14, release date: 2018-03-28, Last modification date: 2024-10-16)

Primary citation

Darwiche, R.,Lugo, F.,Drurey, C.,Varossieau, K.,Smant, G.,Wilbers, R.H.P.,Maizels, R.M.,Schneiter, R.,Asojo, O.A.
Crystal structure of Brugia malayi venom allergen-like protein-1 (BmVAL-1), a vaccine candidate for lymphatic filariasis.
Int. J. Parasitol., 48:371-378, 2018

PubMed Abstract: Brugia malayi is a causative agent of lymphatic filariasis, a major tropical disease. The infective L3 parasite stage releases immunomodulatory proteins including the venom allergen-like proteins (VALs), which are members of the SCP/TAPS (Sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. BmVAL-1 is a major target of host immunity with >90% of infected B. malayi microfilaraemic cases being seropositive for antibodies to BmVAL-1. This study is part of ongoing efforts to characterize the structures and functions of important B. malayi proteins. Recombinant BmVAL-1 was produced using a plant expression system, crystallized and the structure was solved by molecular replacement and refined to 2.1 Å, revealing the characteristic alpha/beta/alpha sandwich topology of eukaryotic SCP/TAPS proteins. The protein has more than 45% loop regions and these flexible loops connect the helices and strands, which are longer than predicted based on other parasite SCP/TAPS protein structures. The large central cavity of BmVAL-1 is a prototypical CRISP cavity with two histidines required to bind divalent cations. The caveolin-binding motif (CBM) that mediates sterol binding in SCP/TAPS proteins is large and open in BmVAL-1 and is N-glycosylated. N-glycosylation of the CBM does not affect the ability of BmVAL-1 to bind sterol in vitro. BmVAL-1 complements the in vivo sterol export phenotype of yeast mutants lacking their endogenous SCP/TAPS proteins. The in vitro sterol-binding affinity of BmVAL-1 is comparable with Pry1, a yeast sterol transporting SCP/TAPS protein. Sterol binding of BmVAL-1 is dependent on divalent cations. BmVAL-1 also has a large open palmitate-binding cavity, which binds palmitate comparably to tablysin-15, a lipid-binding SCP/TAPS protein. The central cavity, CBM and palmitate-binding cavity of BmVAL-1 are interconnected within the monomer with channels that can serve as pathways for water molecules, cations and small molecules.

PubMed: 29501266
DOI: 10.1016/j.ijpara.2017.12.003

Experimental method

X-RAY DIFFRACTION (2.25 Å)