Impact of chemical heterogeneity on protein self-assembly in water
- Authors
- Chong, Song-Ho; Ham, Sihyun
- Issue Date
- May-2012
- Publisher
- NATL ACAD SCIENCES
- Keywords
- solvation thermodynamics; dehydration; protein interface
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.109, no.20, pp 7636 - 7641
- Pages
- 6
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 109
- Number
- 20
- Start Page
- 7636
- End Page
- 7641
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/11904
- DOI
- 10.1073/pnas.1120646109
- ISSN
- 0027-8424
1091-6490
- Abstract
- Hydrophobicity is thought to underlie self-assembly in biological systems. However, the protein surface comprises hydrophobic and hydrophilic patches, and understanding the impact of such a chemical heterogeneity on protein self-assembly in water is of fundamental interest. Here, we report structural and thermodynamic investigations on the dimer formation of full-length amyloid-beta proteins in water associated with Alzheimer's disease. Spontaneous dimerization process-from the individual diffusive regime at large separations, through the approach stage in which two proteins come close to each other, to the structural adjustment stage toward compact dimer formation-was captured in full atomic detail via unguided, explicit-water molecular dynamics simulations. The integral-equation theory of liquids was then applied to simulated protein structures to analyze hydration thermodynamic properties and the water-mediated interaction between proteins. We demonstrate that hydrophilic residues play a key role in initiating the dimerization process. A long-range hydration force of enthalpic origin acting on the hydrophilic residues provides the major thermodynamic force that drives two proteins to approach from a large separation to a contact distance. After two proteins make atomic contacts, the nature of the water-mediated interaction switches from a long-range enthalpic attraction to a short-range entropic one. The latter acts both on the hydrophobic and hydrophilic residues. Along with the direct protein-protein interactions that lead to the formation of intermonomer hydrogen bonds and van der Waals contacts, the water-mediated attraction of entropic origin brings about structural adjustment of constituent monomer proteins toward the formation of a compact dimer structure.
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