Functionality of wrapping defects in soluble proteins: what cannot be kept dry must be conserved.
Soluble proteins preserve their structure only if a sufficient number of non-polar groups are clustered around the backbone hydrogen bonds, protecting them from water attack. When these bonds are not properly wrapped or dehydrated intramolecularly, structural integrity can be preserved through binding partnerships. This is because insufficiently wrapped hydrogen bonds are inherently adhesive and become better shielded upon protein-ligand association. Thus, we postulate that deficiently wrapped hydrogen bonds are functionally relevant. Two findings that support this conjecture are: (a) there is a statistically relevant linear correlation between the number of defects in a folding domain and its proteomic connectivity, obtained from large-scale two-hybrid experiments; (b) the residues paired by under-wrapped hydrogen bonds are highly conserved. The high mutational sensitivity of under-wrapped regions can be rationalized, since their structural integrity relies on their propensity to behave as binding sites, in turn, a consequence of their adhesiveness. Thus, the regions in soluble protein structure that cannot be kept dry in water tend to be conserved.
Fernández
Ariel
A
Indiana University School of Informatics and Center for Computational Biology and Bioinformatics, Indiana University Medical School, 714 N. Senate Avenue Suite 250, Indianapolis, IN 46202, USA.
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D008958:Models, Molecular; D009154:Mutation; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012995:Solubility; D014867:Water / Q000737:chemistry
D000213:Acyl Carrier Protein; D006454:Hemoglobins; D021122:Protein Subunits; D011506:Proteins; D014867:Water