Faculty Collaboration Database

Calcium-induced environmental adaptability of the blood protein vitronectin. Biophys J 2022 Oct 18;121(20):3896-3906

Date

09/04/2022

Pubmed ID

36056555

Pubmed Central ID

PMC9674982

DOI

10.1016/j.bpj.2022.08.044

Scopus ID

2-s2.0-85137693880 (requires institutional sign-in at Scopus site)

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.

Author List

Tian Y, Shin K, Aleshin AE, Im W, Marassi FM

Authors

Francesca M. Marassi PhD Chair, Professor in the Biophysics department at Medical College of Wisconsin
Kyungsoo Shin PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Binding Sites
Calcium
Crystallography, X-Ray
Hemopexin
Protein Binding
Protein Conformation
Vitronectin