A disordered region retains the full protease inhibitor activity and the capacity to induce CD8 + T cells in vivo of the oral vaccine adjuvant U-Omp19.

Autor:	Laura Darriba M; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina., Castro CP; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina., Coria LM; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina., Bruno L; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina., Laura Cerutti M; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina., Otero LH; Fundación Instituto Leloir, IIBBA-CONICET, and Plataforma Argentina de Biología Estructural y Metabolómica PLABEM, Buenos Aires, Argentina., Chemes LB; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina., Rasia RM; Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Santa Fe, Argentina and Plataforma Argentina de Biología Estructural y Metabolómica PLABEM, Buenos Aires, Argentina., Klinke S; Fundación Instituto Leloir, IIBBA-CONICET, and Plataforma Argentina de Biología Estructural y Metabolómica PLABEM, Buenos Aires, Argentina., Cassataro J; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina., Pasquevich KA; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.; Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2022 Sep 06; Vol. 20, pp. 5098-5114. Date of Electronic Publication: 2022 Sep 06 (Print Publication: 2022).
DOI:	10.1016/j.csbj.2022.08.054
Abstrakt:	U-Omp19 is a bacterial protease inhibitor from Brucella abortus that inhibits gastrointestinal and lysosomal proteases, enhancing the half-life and immunogenicity of co-delivered antigens. U-Omp19 is a novel adjuvant that is in preclinical development with various vaccine candidates. However, the molecular mechanisms by which it exerts these functions and the structural elements responsible for these activities remain unknown. In this work, a structural, biochemical, and functional characterization of U-Omp19 is presented. Dynamic features of U-Omp19 in solution by NMR and the crystal structure of its C-terminal domain are described. The protein consists of a compact C-terminal beta-barrel domain and a flexible N-terminal domain. The latter domain behaves as an intrinsically disordered protein and retains the full protease inhibitor activity against pancreatic elastase, papain and pepsin. This domain also retains the capacity to induce CD8 + T cells in vivo of U-Omp19. This information may lead to future rationale vaccine designs using U-Omp19 as an adjuvant to deliver other proteins or peptides in oral formulations against infectious diseases, as well as to design strategies to incorporate modifications in its structure that may improve its adjuvanticity. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KAP, LMC and JC are inventors of a patent related to U-Omp19 “Adjuvant for vaccines, vaccines that comprise it and uses thereof” PCT/ES2010/070667. The owner of this patent is the National Research Council CONICET. The existence of the patent did not have any role in experimental design, data collection and analysis, decision to publish, or preparation of this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2022 The Authors.)
Databáze:	MEDLINE
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