Open AccessNeutral Sites for Calcium Ion Binding to Elastin and Collagen: A Charge Neutralization Theory for Calcification and Its Relationship to Atherosclerosis
Author(s) -
Dan W. Urry
Publication year - 1971
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.68.4.810
Subject(s) - chemistry , calcium , ion , neutralization , elastin , calcification , crystallography , biophysics , stereochemistry , biochemistry , organic chemistry , biology , medicine , pathology , antibody , immunology , genetics
Neutral, uncharged binding sites for calcium ions are proposed for elastin and collagen. The sites utilize, particularly from a conformational viewpoint, the most striking feature of the amino acid composition, that is, the high glycine content. Glycines favor the formation of β-turns and associated conformations that are known, from studies on ion-transporting antibiotics, to interact with cations. By analogy with certain antibiotics, which are uncharged polypeptides and depsipeptides that bind cations by coordination with neutral acyl oxygens, it is proposed that calcium-ion binding also utilizes uncharged coordinating groups, i.e., neutral sites, in the protein matrix. The protein matrix, which becomes positively charged by virtue of the bound calcium ions, attracts neutralizing phosphate and carbonate ions, which then allow further calcium ion binding. The driving force is, therefore, the affinity of calcium ions for the neutral nucleation sites. The charge neutralization theory of calcification suggests a fundamental role of organic anions, for example sulfated mucopolysaccharides, in regulating bone formation and in retardation of atherosclerosis. The proposed mechanism contains elements that tend to unify several theories on the pathogenesis of atherosclerosis.