CRTAC1 has a Compact β-propeller–TTR Core Stabilized by Potassium Ions DOI Creative Commons
J. Wouter Beugelink,

Henrietta Hóf,

B.J.C. Janssen

et al.

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(18), P. 168712 - 168712

Published: July 17, 2024

Cartilage acidic protein-1 (CRTAC1) is a secreted glycoprotein with roles in development, function and repair of the nervous system. It linked to ischemic stroke, osteoarthritis (long) COVID outcomes, has suppressive activity carcinoma bladder cancer. Structural characterization CRTAC1 been complicated by its tendency form disulfide-linked aggregates. Here, we show that stabilized potassium ions. Using x-ray crystallography, determined structure 1.6 Å. This reveals protein consists three-domain fold, including previously-unreported compact β-propeller–TTR combination, which an extended loop TTR plugs β-propeller core. Electron density observed for ten bound ions: six calcium, three one sodium. Low ion concentrations lead changes tryptophan environment exposure two buried free cysteines located on β-blade β-propeller-plugging loop. Mutating serines prevents covalent intermolecular interactions, but not aggregation, absence The binding sites are between blades β-propeller, explaining their importance stability fold. Despite varying sequence, structurally similar conserved features CRTAC family. These insights into provide basis further work health disease.

Language: Английский

CRTAC1 has a Compact β-propeller–TTR Core Stabilized by Potassium Ions DOI Creative Commons
J. Wouter Beugelink,

Henrietta Hóf,

B.J.C. Janssen

et al.

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(18), P. 168712 - 168712

Published: July 17, 2024

Cartilage acidic protein-1 (CRTAC1) is a secreted glycoprotein with roles in development, function and repair of the nervous system. It linked to ischemic stroke, osteoarthritis (long) COVID outcomes, has suppressive activity carcinoma bladder cancer. Structural characterization CRTAC1 been complicated by its tendency form disulfide-linked aggregates. Here, we show that stabilized potassium ions. Using x-ray crystallography, determined structure 1.6 Å. This reveals protein consists three-domain fold, including previously-unreported compact β-propeller–TTR combination, which an extended loop TTR plugs β-propeller core. Electron density observed for ten bound ions: six calcium, three one sodium. Low ion concentrations lead changes tryptophan environment exposure two buried free cysteines located on β-blade β-propeller-plugging loop. Mutating serines prevents covalent intermolecular interactions, but not aggregation, absence The binding sites are between blades β-propeller, explaining their importance stability fold. Despite varying sequence, structurally similar conserved features CRTAC family. These insights into provide basis further work health disease.

Language: Английский

Citations

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