Assessment of helical interfaces in protein-protein interactions

Abstract

Herein we identify and analyze helical protein interfaces as potential targets for synthetic modulators of protein-protein interactions.

Fig. 1

The α-helix is a ubiquitous element in biomolecular recognition. (a) MATa1/MATα2-3A heterodimer bound to DNA (PDB code: 1LE8), (b) complex of the WH2 domain of WAVE with Actin-DNAse I (PDB code: 2A40), (c) endothelial nitric oxide synthase peptide bound to calmodulin (PDB code: 1NIW).

Fig. 2

Stabilized helices and non-natural helix mimetics: several strategies that stabilize the R-helical conformation in peptides or mimic this domain with non-natural scaffolds have been described. Efforts include β-peptide helices, terphenyls, miniproteins, peptoids and side-chain and backbone (hydrogen bond surrogate, HBS) crosslinked α-helices.^–

Fig. 3

Evaluation of structures from the Protein Data Bank to identify and assess helical interfaces in protein–protein (HIPP) interactions.

Fig. 4

(a) Fraction of the current Protein Data Bank involved in helical interfaces. (b) Classification of proteins displaying helical interfaces by function.

Fig. 5

Distribution of helix length at protein interfaces. The present analysis suggests an average length of 14 residues for helices participating in interfaces.