The multilayered organization of water-soluble proteins

Abstract

The structural analysis of proteins has focused primarily on secondary structure, three-dimensional fold and active site while whole surface has been analyzed to a lesser extent and interior has not received much attention. Here we present an analysis of both the surfaces and the interiors of a set of water-soluble monomeric proteins in terms of solvent-excluded surface (SES) and atomic partial charge. The analysis shows that the surface of a soluble monomer has a net negative charge and is much smoother than the interior. Most interestingly with regard to both atomic partial charge and SES-defined geometric property there exists a multilayered organization from the exterior to the interior of a soluble monomer. The multilayered organization is closely related to protein-solvent interaction and should be a general feature of a water-soluble protein. Particularly the multilayered organization may set an upper limit for the size of a water-soluble monomer and plays an important role in the determination of its overall shape in solution. Significance statementThe analysis of the solvent-excluded surfaces (SESs) of a large set of water-soluble monomers with crystal structures shows that in any soluble monomer there exists a multilayered organization in terms of SES-defined electric and geometric properties. It means that the atoms in a soluble monomer are not randomly distributed but organized into successive layers to optimize its interaction with solvent molecules. The SES-derived multi-layered organization should be a general feature of a water-soluble protein and likely plays a vital role in its solvation, folding and structure.