The surface of beta-sheet proteins contains amphiphilic regions which may provide clues about protein folding.
A major bottleneck in the field of biochemistry is our limited understanding of the processes by which a protein folds into its native conformation. Much of the work on this issue has focused on the conserved core of the folded protein. However, one might imagine that a ubiquitous motif for unaided folding or for the recognition of chaperones may involve 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 proteins. All proteins, including beta-sheet proteins, contain regions with amphiphilic alpha-helical potential. That is, any alpha-helix formed by that region would be amphiphilic, having both hydrophobic and hydrophilic surfaces. In the three-dimensional structure of all beta-sheet proteins analyzed, we have found a distinct pattern in the spatial distribution of sequences with amphiphilic alpha-helical potential. The amphiphilic regions occur in ring shaped clusters approximately 20 to 30 A in diameter on the surface of the protein. In addition, these regions have a strong preference for positively charged amino acids and a lower preference for residues not favorable to alpha-helix formation. Although the purpose of these amphiphilic regions which are not associated with naturally occurring alpha-helix is unknown, they may play a critical role in highly conserved processes such as protein folding.
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