Structural insights into a functional unit from an immunogenic mollusk hemocyanin

Sebastián M. Muñoz; Gabriel Vallejos-Baccelliere; Augusto Manubens; Michelle L. Salazar; Andrey F.Z. Nascimento; Patricio Tapia-Reyes; Claudio Meneses; Andre L.B. Ambrosio; María Inés Becker; Victoria Guixé; Victor Castro-Fernandez

Keywords: glycosylation, concholepas concholepas, functional unit, mollusk hemocyanin, oxygen binding-protein

Abstract

Mollusk hemocyanins, among the largest known proteins, are used as immunostimulants in biomedical and clinical applications. The hemocyanin of the Chilean gastropod Concholepas concholepas (CCH) exhibits unique properties, which makes it safe and effective for human immunotherapy, as observed in animal models of bladder cancer and melanoma, and dendritical cell vaccine trials. Despite its potential, the structure and amino acid sequence of CCH remain unknown. This study reports two sequence fragments of CCH, representing three complete functional units (FUs). We also determined the high-resolution (1.5 Å) X-ray crystal structure of an "FU-g type" from the CCHB subunit. This structure enables in-depth analysis of chemical interactions at the copper-binding center and unveils an unusual, truncated N-glycosylation pattern. These features are linked to eliciting more robust immunological responses in animals, offering insights into CCH's enhanced immunostimulatory properties and opening new avenues for its potential applications in biomedical research and therapies.

Más información

Título de la Revista: STRUCTURE
Volumen: 32
Número: 6
Editorial: Cell Press
Fecha de publicación: 2024
Página de inicio: 812
Página final: 823
Idioma: Inglés
URL: https://pubmed.ncbi.nlm.nih.gov/38513659/