THE SURFACE OF BETA-SHEET PROTEINS CONTAINS AMPHIPHILIC REGIONS WHICHMAY PROVIDE CLUES ABOUT PROTEIN-FOLDING

A major bottleneck in the field of biochemistry is our limited underst anding of the processes by which a protein folds into its native confo rmation, Much of the work on this issue has focused on the conserved c ore of the folded protein. However, one might imagine that a ubiquitou s moth for unaided folding or for the recognition of chaperones may in volve regions on the surface of the native structure. We explore this possibility by an analysis of the spatial distribution of regions with amphiphilic alpha-helical potential on the surface of beta-sheet prot eins, All proteins, including beta-sheet proteins, contain regions wit h amphiphilic alpha-helical potential, That is, any alpha-helix formed by that region would be amphiphilic, having both hydrophobic and hydr ophilic surfaces. In the three-dimensional structure of all beta-sheet proteins analyzed, we have found a distinct pattern in the spatial di stribution of sequences with amphiphilic alpha-helical potential, The amphiphilic regions occur in ring shaped clusters approximately 20 to 30 Angstrom in diameter on the surface of the protein, In addition, th ese regions have a strong preference for positively charged amino acid s and a lower preference for residues not favorable to alpha-helix for mation. Although the purpose of these amphiphilic regions which are no t associated with naturally occurring alpha-helix is unknown, they may play a critical role in highly conserved processes such as protein fo lding. (C) 1996 Wiley-Liss, Inc.