PDBsum entry 3c3h

De novo protein

PDB id: 3c3h

Contents

Protein chain

34 a.a.

Waters ×13

PDB id:

3c3h

Name:

De novo protein

Title:

Alpha/beta-peptide helix bundles: a gcn4-pli analogue with an (alpha- alpha-beta) backbone and cyclic beta residues

Structure:

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. Chain: a. Engineered: yes

Source:

Synthetic: yes. Other_details: synthetic peptide

Resolution:

2.20Å R-factor: 0.235 R-free: 0.278

Authors:

W.S.Horne,J.L.Price,S.H.Gellman

Key ref:

W.S.Horne et al. (2008). Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly. Proc Natl Acad Sci U S A, 105, 9151-9156. PubMed id: 18587049 DOI: 10.1073/pnas.0801135105

Date:

28-Jan-08 Release date: 17-Jun-08

Protein chain

No UniProt id for this chain

Struc: 33 a.a.

DOI no: 10.1073/pnas.0801135105

Proc Natl Acad Sci U S A 105:9151-9156 (2008)

PubMed id: 18587049

Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly.

W.S.Horne, J.L.Price, S.H.Gellman.

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.

Selected figure(s)

Figure 1.
Chemical structures and helical wheel diagrams of 1–9. (A) Primary sequences of α-peptide 1 and α/β-peptides 2–9, sorted according to α/β backbone pattern. Bold letters indicate hydrophobic core residues in the GCN4-pLI sequence. Colored circles indicate sequence positions occupied by β-residues, cyan for β^3-residues and orange for cyclic β-residues. (B) Helical wheel diagram of 1 with hydrophobic core residues indicated. (C) Structures of an α-amino acid, a β^3-amino acid, and the cyclic β-amino acids ACPC (X) and APC (Z). (D) Helical wheel diagrams of the α/β residue patterns of 2–9 based on a heptad repeat. Each circle represents a residue and is colored by residue type, yellow for α-residues, cyan for β^3-residues, and orange for cyclic β-residues. Bold circles indicate hydrophobic core positions.

Figure 2.
Comparison of the GCN4-pLI side chain sequence on four different backbone patterns. (A) Helix bundle quaternary structures of each derivative with yellow and blue indicating α- and β^3-residues, respectively. (B) Helical secondary structures of each α/β-peptide 2–4 (red) compared with that of α-peptide 1 (yellow); the overlays and accompanying RMSD values are based on C[α] atoms in shared α-residues. The coordinates for 1 (PDB: 1GCL) (21) and 2 (PDB: 2OXK) (14) were obtained from previously published structures.

Figures were selected by the author.