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Anisotropic Membrane Curvature Sensing by Amphipathic Peptides
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.ORCID-id: 0000-0003-4114-8768
Antal upphovsmän: 32016 (Engelska)Ingår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 110, nr 1, s. 197-204Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Many proteins and peptides have an intrinsic capacity to sense and induce membrane curvature, and play crucial roles for organizing and remodeling cell membranes. However, the molecular driving forces behind these processes are not well understood. Here, we describe an approach to study curvature sensing by simulating the interactions of single molecules with a buckled lipid bilayer. We analyze three amphipathic antimicrobial peptides, a class of membrane-associated molecules that specifically target and destabilize bacterial membranes, and find qualitatively different sensing characteristics that would be difficult to resolve with other methods. Our findings provide evidence for direction-dependent curvature sensing mechanisms in amphipathic peptides and challenge existing theories of hydrophobic insertion. The buckling approach is generally applicable to a wide range of curvature-sensing molecules, and our results provide strong motivation to develop new experimental methods to track position and orientation of membrane proteins.

Ort, förlag, år, upplaga, sidor
2016. Vol. 110, nr 1, s. 197-204
Nationell ämneskategori
Biofysik
Forskningsämne
biofysik
Identifikatorer
URN: urn:nbn:se:su:diva-126377DOI: 10.1016/j.bpj.2015.11.3512ISI: 000367783900012PubMedID: 26745422OAI: oai:DiVA.org:su-126377DiVA, id: diva2:902970
Tillgänglig från: 2016-02-12 Skapad: 2016-02-01 Senast uppdaterad: 2022-02-23Bibliografiskt granskad
Ingår i avhandling
1. A computational approach to curvature sensing in lipid bilayers
Öppna denna publikation i ny flik eller fönster >>A computational approach to curvature sensing in lipid bilayers
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Local curvature is a key driving force for spatial organization of cellular membranes, via a phenomenon known as membrane curvature sensing, where the binding energy of membrane associated macromolecules depends on the local membrane shape. However, the microscopic mechanisms of curvature sensing are not well understood. Molecular dynamics simulations offer a powerful complement to biochemical experiments, yet their contribution to the study of curvature sensing has been limited, due in part to the lack of efficient methods, not least because of methodological difficulties in dealing with curved membranes. We develop a method based on simulated buckling, which has been previously employed to study mechanical properties of membranes. Here, we describe, validate and evaluate this method. We then apply to study curvature sensing properties of three model systems, using coarse-grained simulations. On the first system, we study lipid sorting in a three-component lipid mixture with emphasis on cardiolipin. We find that if curvature is high, curvature sensing is strong enough to drive cardiolipin molecules to negative curvature regions, outcompeting other lipids, without the need of external interactions or cooperative effects. We then simulated three systems consisting of a short amphipathic peptide attached to the surface of a buckled membrane. All three peptides localize to positive curvature, in agreement with the so-called cylindrical hydrophobic insertion mechanism. Their orientational preferences, however, defy the prediction of alignment perpendicular to the direction of maximum curvature. They also fail to show expected symmetries, indicating there is more to the picture than purely shape-based effects. The curvature sensing probe of the next system is a transmembrane trimeric protein, which shows preference to intermediate curvature, in agreement with theoretical predictions. But the lack of an expected 2-fold rotation symmetry indicates that the trimer senses the local curvature gradient, and not just the point-wise local curvature. Finally, dispensing with the buckling methodology, we simulated a series of symmetric transmembrane multimers embedded in cylindrical bilayers. Based on the results of these simulations and theoretical arguments, we discuss the relationship between structural symmetry and curvature sensitivity. We conclude that anisotropic (i.e. orientation-dependent) curvature sensing is strongly limited by odd and high order rotational symmetries. However, measurements of in-plane orientation on peptides and asymmetric proteins, as well as dimers and tetramers, should yield valuable information. Our method, along with our initial conclusions, provides an useful tool for the understanding of the relationship between membrane shape and membrane protein function, and should prove useful to biophysicists in the design and interpretation of experimental curvature sensing assays.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2018. s. 60
Nyckelord
curvature sensing, membrane curvature, cardiolipin, amphipathic helix, symmetric multimers, lipid bilayer, molecular dynamics
Nationell ämneskategori
Biofysik
Forskningsämne
biofysik
Identifikatorer
urn:nbn:se:su:diva-157417 (URN)978-91-7797-332-4 (ISBN)978-91-7797-333-1 (ISBN)
Disputation
2018-09-07, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 14:00 (Engelska)
Opponent
Handledare
Anmärkning

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 4: Manuscript.

Tillgänglig från: 2018-08-15 Skapad: 2018-06-18 Senast uppdaterad: 2022-02-26Bibliografiskt granskad

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Elías-Wolff, Federico

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