Structural insights into a functional unit from an immunogenic mollusk hemocyanin

被引:2
|
作者
Munoz, Sebastian M. [1 ]
Vallejos-Baccelliere, Gabriel [1 ]
Manubens, Augusto [2 ,3 ]
Salazar, Michelle L. [3 ]
Nascimento, Andrey F. Z. [4 ]
Tapia-Reyes, Patricio [5 ,6 ]
Meneses, Claudio [6 ,7 ,8 ,9 ]
Ambrosio, Andre L. B. [1 ,10 ]
Becker, Maria Ines [2 ,3 ]
Guixe, Victoria [1 ]
Castro-Fernandez, Victor [1 ]
机构
[1] Univ Chile, Fac Ciencias, Dept Biol, Lab Bioquim & Biol Mol, Santiago 780003, Chile
[2] Biosonda Corp, Dept Invest & Desarrollo, Santiago 7750629, Chile
[3] Fdn Ciencia & Tecnol Desarrollo FUCITED, Santiago 7750629, Chile
[4] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, BR-13083970 Campinas, SP, Brazil
[5] Univ Santo Tomas, Fac Ciencias, Escuela Biotecnol, Santiago 8370003, Chile
[6] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Santiago 8331150, Chile
[7] Pontificia Univ Catolica Chile, Fac Agron & Sistemas Nat, Dept Fruticultura & Enol, Santiago 7820436, Chile
[8] Millennium Nucleus Dev Super Adaptable Plants MN S, Santiago 8331150, Chile
[9] Millennium Inst, Ctr Genome Regulat CRG, Santiago 8331150, Chile
[10] Univ Sao Paulo, Sao Carlos Inst Phys IFSC, BR-13563120 Sao Carlos, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
CRYO-EM STRUCTURE; CONCHOLEPAS HEMOCYANIN; N-GLYCANS; CARBOHYDRATE CHAINS; CRYSTAL-STRUCTURE; MOLECULAR-MODEL; SUBUNIT; REVEALS; KLH; INTERFACES;
D O I
10.1016/j.str.2024.02.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 A & ring; ) 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.
引用
收藏
页码:812 / 823.e4
页数:17
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