Structural and Functional Highlights of Vacuolar Soluble Protein 1 from Pathogen Trypanosoma brucei brucei.
Trypanosoma brucei (T. brucei) is responsible for the fatal human disease called African trypanosomiasis, or sleeping sickness. The causative parasite, Trypanosoma, encodes soluble versions of inorganic pyrophosphatases (PPase), also called vacuolar soluble proteins (VSPs), which are localized to its acidocalcisomes. The latter are acidic membrane-enclosed organelles rich in polyphosphate chains and divalent cations whose significance in these parasites remains unclear. We here report the crystal structure of T. brucei brucei acidocalcisomal PPases in a ternary complex with Mg(2+) and imidodiphosphate. The crystal structure reveals a novel structural architecture distinct from known class I PPases in its tetrameric oligomeric state in which a fused EF hand domain arranges around the catalytic PPase domain. This unprecedented assembly evident from TbbVSP1 crystal structure is further confirmed by SAXS and TEM data. SAXS data suggest structural flexibility in EF hand domains indicative of conformational plasticity within TbbVSP1.
From the Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
Abhishek
A
Jamwal
the European Molecular Biology Laboratory, Grenoble Outstation, 38042 Grenoble, France, the Unit for Virus Host-Cell Interactions, University Grenoble Alpes-EMBL-CNRS, 38042 Grenoble, France, and.
Adam R
AR
Round
the IMPMC, UMR 7590, CNRS-UPMC-IRD, 75252 Paris, France.
Ludovic
L
Bannwarth
the IMPMC, UMR 7590, CNRS-UPMC-IRD, 75252 Paris, France.
Catherine
C
Venien-Bryan
the European Molecular Biology Laboratory, Grenoble Outstation, 38042 Grenoble, France, the Unit for Virus Host-Cell Interactions, University Grenoble Alpes-EMBL-CNRS, 38042 Grenoble, France, and.
Hassan
H
Belrhali
From the Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
Manickam
M
Yogavel
From the Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India, amit.icgeb@gmail.com.
Amit
A
Sharma
D018360:Crystallography, X-Ray; D006801:Humans; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011755:Pyrophosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*
D015800:Protozoan Proteins; D011755:Pyrophosphatases; C482344:VSP1 protein, Trypanosoma brucei
Trypanosoma brucei; crystal structure; electron microscopy (EM); isothermal titration calorimetry (ITC); small-angle x-ray scattering (SAXS)