Structural distribution of dipeptides that are identified to be determinants of intracellular protein stability.
The dipeptides that had been previously implicated as determinants of in vivo protein stability (Guruprasad, K., Reddy, B.V.B. and Pandit, M.W., 1990. Protein Eng. 4, 155-161) have been reassessed on a latest data set and about 25% dipeptide combinations (102 dipeptides) were found to play significant role in determining the intracellular protein stability. These were classified as stabilizing dipeptides (Stb), destabilizing dipeptides (Dst) and normal dipeptides (Nor). By different theoretical approaches we have investigated the global localization of these dipeptides in a set of 303 best resolved (< or = 2.0A) non-homologous X-ray defined protein structures. The Dst dipeptides are found to be more of hydrophilic combinations where as Stb dipeptides are more of hydrophobic combinations. We observed a significant difference in overall frequency of occurrence of Stb and Dst dipeptides in different secondary structural regions. The sensitive dipeptides (Stb + Dst) are less in beta-strands and more in coils. A high frequency of occurrence of Stb are observed in the regions closer to the molecular surface compared to the Dst and Nor dipeptides. A significantly high dipole interactions are observed in the Dst dipeptides. The studies indicate that though the Dst dipeptides are more of hydrophilic nature they are localized significantly more in the buried regions of protein structures, on the other hand Stb are more of hydrophobic nature but relatively more accessible to the solvent. These dipeptides therefore increasing sensitivity of the protein to external environment, any alteration in their occurrence in the sequence could increase or decrease intracellular stability of the protein. These observations are useful to select mutations to alter intracellular stability of a given protein and therefore have implications in protein engineering.
Centre for Cellular and Molecular Biology Hyderabad, India. bvbreddy@ccmb.globemail.com
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Reddy
D001665:Binding Sites; D004151:Dipeptides / Q000737:chemistry / Q000145:classification* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry
D004151:Dipeptides; D012997:Solvents