Architectonic principles of polyproline II helix bundle protein domains

• Published in: Archives of biochemistry and biophysics Vol. 756; p. 109981
• Main Authors: Rodríguez, Cristian Segura, Laurents, Douglas V.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Flanking sequence; Hydrogen bond; Macrodipoles; Peptide assembly; Polyproline II helix bundles; Peptide assembly; Macrodipoles; Flanking sequence; Polyproline II helix bundles; Hydrogen bond
• ISSN: 0003-9861; 1096-0384; 1096-0384
• DOI: 10.1016/j.abb.2024.109981

Glycine rich polyproline II helix assemblies are an emerging class of natural domains found in several proteins with different functions and diverse origins. The distinct properties of these domains relative to those composed of α-helices and β-sheets could make glycine-rich polyproline II helix assemblies a useful building block for protein design. Whereas the high population of polyproline II conformers in disordered state ensembles could facilitate glycine-rich polyproline II helix folding, the architectonic bases of these structures are not well known. Here, we compare and analyze their structures to uncover common features. These protein domains are found to be highly tolerant of distinct flanking sequences. This speaks to the robustness of this fold and strongly suggests that glycine rich polyproline II assemblies could be grafted with other protein domains to engineer new structures and functions. These domains are also well packed with few or no cavities. Moreover, a significant trend towards antiparallel helix configuration is observed in all these domains and could provide stabilizing interactions among macrodipoles. Finally, extensive networks of Cα-H···OC hydrogen bonds are detected in these domains. Despite their diverse evolutionary origins and activities, glycine-rich polyproline II helix assemblies share architectonic features which could help design novel proteins. [Display omitted] •Several natural protein domains are composed of glycine-rich PPII helix bundles.•We find that they lack cavities and prefer anti-parallel helix orientations.•These bundles are tolerant of diverse flanking sequences.•Rich inter-helical NH··OC and CαH··OC H-bond networks are present.