Structural analysis of an Echinococcus granulosus actin-fragmenting protein by small-angle x-ray scattering studies and molecular modeling.
The Echinococcus granulosus actin filament-fragmenting protein (EgAFFP) is a three domain member of the gelsolin family of proteins, which is antigenic to human hosts. These proteins, formed by three or six conserved domains, are involved in the dynamic rearrangements of the cytoskeleton, being responsible for severing and capping actin filaments and promoting nucleation of actin monomers. Various structures of six domain gelsolin-related proteins have been investigated, but little information on the structure of three domain members is available. In this work, the solution structure of the three domain EgAFFP has been investigated through small-angle x-ray scattering (SAXS) studies. EgAFFP exhibits an elongated molecular shape. The radius of gyration and the maximum dimension obtained by SAXS were, respectively, 2.52 +/- 0.01 nm and 8.00 +/- 1.00 nm, both in the absence and presence of Ca2+. Two different molecular homology models were built for EgAFFP, but only one was validated through SAXS studies. The predicted structure for EgAFFP consists of three repeats of a central beta-sheet sandwiched between one short and one long alpha-helix. Possible implications of the structure of EgAFFP upon actin binding are discussed.
Laboratório de Biologia Molecular de Cestódeos, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil.
Eliana D
ED
Grimm
Rodrigo V
RV
Portugal
Mário
M
de Oliveira Neto
Nádia H
NH
Martins
Igor
I
Polikarpov
Arnaldo
A
Zaha
Henrique B
HB
Ferreira
D000818:Animals; D003198:Computer Simulation; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D048209:Echinococcus granulosus / Q000737:chemistry* / Q000235:genetics; D018260:Gelsolin / Q000737:chemistry; D006736:Horses; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012542:Scattering, Radiation; D040681:Structural Homology, Protein; D014965:X-Rays
D003598:Cytoskeletal Proteins; D018260:Gelsolin; D011994:Recombinant Proteins; C028514:actin-modulating proteins