Effect Of Ions On Chicken Cystatin C Structure Using Molecular Dynamics Simulations

Cystatins, as a kind of reversible, competitive, physiological inhibitors of cysteine proteases, are widely distributed in various animal and plant tissues. Cystatins have important physiological role in organism, and they participate in many kinds of physiologies and the pathology process. The L68Q variant of human cystatin c is the causative agent of Hereditary Cystatin C Amyloid Angiopathy (HCCAA), which is a dominantly inherited disorder characterized by tissue deposition of amyloid fibrils in blood vessels. The pathogenic mechanism of cystatin is very similar as other neurodegenerative diseases such as mad cow disease, Parkinson`s disease and Alzheimer`s diseases. Cystatin monomers can form highly domain-swapped dimmers, thus forming part of the amyloidgenic deposits, which may lead to fatal cerebral hemorrhage. Previous study had shown that magnesium chloride can reduce the structural stability of cystatin.In this paper, we performed five 10-ns molecular dynamics simulations with different ions in order to check the differences of protein structure. We found that the ions could change the structure of cystatin and reduce the structural stability. The ions broken the hydrogen bonds, salt-bridges and disulfides of cystatin while relaxed the hydrophobic core of cystatin, which reduced the structural stability of cystatin. This study can be very helpful to illustrate the mechanism of effections of ions on cystatin structural stability.