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Calcium-induced environmental adaptability of the blood protein vitronectin.


ABSTRACT: 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.

SUBMITTER: Tian Y 

PROVIDER: S-EPMC9674982 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Calcium-induced environmental adaptability of the blood protein vitronectin.

Tian Ye Y   Shin Kyungsoo K   Aleshin Alexander E AE   Im Wonpil W   Marassi Francesca M FM  

Biophysical journal 20220902 20


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 Ca<sup>2+</sup> to adapt to excursions of temperature and shear stress. Using X-ray crystallography, molecular dynamics simulations, NMR, and differential scanning fluorimetry, we describe how Ca<sup>2+</sup> and its flexible hydration shell enable the protein to perform conformational changes that re  ...[more]

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