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Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices that enhance protein functionality.

ABSTRACT: Formally annotated π-helices are rare in protein structures but have been correlated with functional sites. Here, we analyze protein structures to show that π-helices are the same as structures known as α-bulges, α-aneurisms, π-bulges, and looping outs, and are evolutionarily derived by the insertion of a single residue into an α-helix. This newly discovered evolutionary origin explains both why π-helices are cryptic, being rarely annotated despite occurring in 15% of known proteins, and why they tend to be associated with function. An analysis of π-helices in the diverse ferritin-like superfamily illustrates their tendency to be conserved in protein families and identifies a putative π-helix-containing primordial precursor, a "missing link" intermediary form of the ribonucleotide reductase family, vestigial π-helices, and a novel function for π-helices that we term a "peristaltic-like shift." This new understanding of π-helices paves the way for this generally overlooked motif to become a noteworthy feature that will aid in tracing the evolution of many protein families, guide investigations of protein and π-helix functionality, and contribute additional tools to the protein engineering toolkit.

SUBMITTER: Cooley RB

PROVIDER: S-EPMC2981643 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices that enhance protein functionality.

Cooley Richard B RB Arp Daniel J DJ Karplus P Andrew PA

Journal of molecular biology 20101001 2

Formally annotated π-helices are rare in protein structures but have been correlated with functional sites. Here, we analyze protein structures to show that π-helices are the same as structures known as α-bulges, α-aneurisms, π-bulges, and looping outs, and are evolutionarily derived by the insertion of a single residue into an α-helix. This newly discovered evolutionary origin explains both why π-helices are cryptic, being rarely annotated despite occurring in 15% of known proteins, and why the ...[more]

PMID: 20888342

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Dataset Information

Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices that enhance protein functionality.

Publications

Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices that enhance protein functionality.

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