Abstract
Single alpha helices (SAHs) stable in isolated form are often found in motor proteins where they bridge functional domains. Understanding the mechanical response of SAHs is thus critical to understand their function. The quasi-static force-extension relation of a small number of SAHs is known from single-molecule experiments. Unknown, or still controversial, are the molecular scale details behind those observations. We show that the deformation mechanism of SAHs pulled from the termini at pull speeds approaching the quasi-static limit differs from that of typical helices found in proteins, which are stable only when interacting with other protein domains. Using molecular dynamics simulations with atomistic resolution at low pull speeds previously inaccessible to simulation, we show that SAHs start unfolding from the termini at all pull speeds we investigated. Unfolding proceeds residue-by-residue and hydrogen bond breaking is not the main event determining the barrier to unfolding. We use the molecular simulation data to test the cooperative sticky chain model. This model yields excellent fits of the force-extension curves and quantifies the distance, xE = 0.13 nm, to the transition state, the natural frequency of bond vibration, ν0 = 0.82 ns-1, and the height, V0 = 2.9 kcal mol-1, of the free energy barrier associated with the deformation of single residues. Our results demonstrate that the sticky chain model could advantageously be used to analyze experimental force-extension curves of SAHs and other biopolymers.
Highlights
Single alpha helices (SAHs) differ from most helices found in proteins: whereas most protein helices are metastable and short-lived in the absence of intra- or intermolecular interactions with other protein domains, SAHs maintain a stable helical configuration in aqueous solution in the absence of interactions with other biomacromolecules
We show that the deformation mechanism of SAHs pulled from the termini at pull speeds approaching the quasi-static limit differs from that of typical helices found in proteins, which are stable only when interacting with other protein domains
Our simulations indicate that the deformation mechanism of SAHs under applied tension is highly cooperative at all pull speeds tested: because the free energy penalty for creating
Summary
Single alpha helices (SAHs) differ from most helices found in proteins: whereas most protein helices are metastable and short-lived in the absence of intra- or intermolecular interactions with other protein domains, SAHs maintain a stable helical configuration in aqueous solution in the absence of interactions with other biomacromolecules. SAHs have been found in the proteomes of bacteria, archaea and eukaryotes.[1,2,3,4] They are typical components of motor proteins, where they act as spacer or connector segments between globular domains,[1,2,5,6] and could realize similar functions in artificial materials. Clarifying the properties of SAHs is important to understand the functioning of motor proteins and for their targeted application in materials science. Natural SAHs typically contain a large fraction of positively and negatively charged amino acids, and (i, i + 3) or (i, i + 4) salt bridges (where i denotes the position of an amino acid in the linear amino acid sequence) are thought to be important for their thermodynamic stability.[7,8] The pattern of positively and negatively charged amino acids is not indispensable for SAH formation, : polyglutamic acid[9] and polylysine[10,11] form SAHs at pH levels where the side chain residues are uncharged
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