κ-helix and the helical lock and key model: A pivotal way of looking at polyproline II

Tomer Meirson, David Bomze, Gal Markel, Abraham O. Samson

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Motivation: Polyproline II (PPII) is a common conformation, comparable to α-helix and β-sheet. PPII, recently termed with a more generic name - κ-helix, adopts a left-handed structure with 3-fold rotational symmetry. Lately, a new type of binding mechanism - the helical lock and key model was introduced in SH3-domain complexes, where the interaction is characterized by a sliding helical pattern. However, whether this binding mechanism is unique only to SH3 domains is unreported. Results: Here, we show that the helical binding pattern is a universal feature of the κ-helix conformation, present within all the major target families - SH3, WW, profilin, MHC-II, EVH1 and GYF domains. Based on a geometric analysis of 255 experimentally solved structures, we found that they are characterized by a distinctive rotational angle along the helical axis. Furthermore, we found that the range of helical pitch varies between different protein domains or peptide orientations and that the interaction is also represented by a rotational displacement mimicking helical motion. The discovery of rotational interactions as a mechanism, reveals a new dimension in the realm of protein-protein interactions, which introduces a new layer of information encoded by the helical conformation. Due to the extensive involvement of the conformation in functional interactions, we anticipate our model to expand the current molecular understanding of the relationship between protein structure and function.

Original languageEnglish
Pages (from-to)3726-3732
Number of pages7
JournalBioinformatics
Volume36
Issue number12
DOIs
StatePublished - 1 Jun 2020

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© 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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