3C3H

alpha/beta-Peptide helix bundles: A GCN4-pLI analogue with an (alpha-alpha-beta) backbone and cyclic beta residues

Summary for 3C3H

• Entry DOI: 10.2210/pdb3c3h/pdb
• Related: 1GCL 1UO2 2OXK 3C3F 3C3G
• Descriptor: alpha/beta-peptide based on the GCN4-pLI side chain sequence, with an (alpha-alpha-beta) backbone and cyclic beta-residues at positions 1, 4, 10, 19, 22, and 28 (2 entities in total)
• Functional Keywords: helix bundle, foldamer, alpha/beta-peptide, unknown function, de novo protein
• Total number of polymer chains: 1
• Total formula weight: 4024.90

Authors

Horne, W.S.,Price, J.L.,Gellman, S.H. (deposition date: 2008-01-28, release date: 2008-06-17, Last modification date: 2024-07-10)

Primary citation

Horne, W.S.,Price, J.L.,Gellman, S.H.
Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly.
Proc.Natl.Acad.Sci.Usa, 105:9151-9156, 2008

PubMed Abstract: The extent to which polypeptide conformation depends on side-chain composition and sequence has been widely studied, but less is known about the importance of maintaining an alpha-amino acid backbone. Here, we examine a series of peptides with backbones that feature different repeating patterns of alpha- and beta-amino acid residues but an invariant side-chain sequence. In the pure alpha-backbone, this sequence corresponds to the previously studied peptide GCN4-pLI, which forms a very stable four-helix bundle quaternary structure. Physical characterization in solution and crystallographic structure determination show that a variety of alpha/beta-peptide backbones can adopt sequence-encoded quaternary structures similar to that of the alpha prototype. There is a loss in helix bundle stability upon beta-residue incorporation; however, stability of the quaternary structure is not a simple function of beta-residue content. We find that cyclically constrained beta-amino acid residues can stabilize the folds of alpha/beta-peptide GCN4-pLI analogues and restore quaternary structure formation to backbones that are predominantly unfolded in the absence of cyclic residues. Our results show a surprising degree of plasticity in terms of the backbone compositions that can manifest the structural information encoded in a sequence of amino acid side chains. These findings offer a framework for the design of nonnatural oligomers that mimic the structural and functional properties of proteins.

PubMed: 18587049
DOI: 10.1073/pnas.0801135105

Experimental method

X-RAY DIFFRACTION (2.2 Å)