Calcium-induced environmental adaptability of the blood protein vitronectin.

Ye Tian, Kyungsoo Shin, Alexander E Aleshin, Wonpil Im, Francesca M Marassi

Biophysical journal 2022 Oct 18

filter terms:

The adaptability of proteins to their work environments is fundamental for cellular life. Here, we describe how the hemopexin-like domain of the multifunctional blood glycoprotein vitronectin binds Ca2+ to adapt to excursions of temperature and shear stress. Using X-ray crystallography, molecular dynamics simulations, NMR, and differential scanning fluorimetry, we describe how Ca2+ and its flexible hydration shell enable the protein to perform conformational changes that relay beyond the calcium-binding site and alter the number of polar contacts to enhance conformational stability. By means of mutagenesis, we identify key residues that cooperate with Ca2+ to promote protein stability, and we show that calcium association confers protection against shear stress, a property that is advantageous for proteins that circulate in the vasculature, like vitronectin. Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Citation

Ye Tian, Kyungsoo Shin, Alexander E Aleshin, Wonpil Im, Francesca M Marassi. Calcium-induced environmental adaptability of the blood protein vitronectin. Biophysical journal. 2022 Oct 18;121(20):3896-3906