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NMR Investigations of Peptide-Membrane Interactions, Modulation of Peptide-Lipid Interaction as a Switch in Signaling across the Lipid Bilayer
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. (Mäler group)
2010 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

The complexity of multi cellular organisms demands systems that facilitate communicationbetween cells. The neurons in our brains for instance are specialized in this cell-cellcommunication. The flow of ions, through their different ion channels, across the membrane, isresponsible for almost all of the communication between neurons in the brain by changing theneurons membrane potentials. Voltage-gated ion channels open when a certain thresholdpotential is reached. This change in membrane potential is detected by voltage-sensors in the ionchannels. In this licentiate thesis the Homo sapiens voltage- and calcium-gated BK potassiumchannel (HsapBK) has been studied. The NMR solution structure of the voltage-sensor ofHsapBK was solved to shed light upon the voltage-gating in these channels. Structures of othervoltage-gated potassium channels (Kv) have been determined by other groups, enablingcomparison among different types of Kv channels. Interestingly, the peptide-lipid interactions ofthe voltage-sensor in HsapBK are crucial for its mechanism of action.Uni cellular organisms need to sense their environment too, to be able to move towardsmore favorable areas and from less favorable ones, and to adapt their gene profiles to currentcircumstances. This is accomplished by the two-component system, comprising a sensor proteinand a response regulator. The sensor protein transfers signals across the membrane to thecytoplasm. Many sensor proteins contain a HAMP domain close to the membrane that isinvolved in transmitting the signal. The mechanism of this transfer is not yet revealed. Ourstudies show that HAMP domains can be divided into two groups based on the membraneinteraction of their AS1 segments. Further, these two groups are suggested to work by differentmechanisms; one membrane-dependent and one membrane-independent mechanism.Both the voltage-gating mechanism and the signal transduction carried out by HAMPdomains in the membrane-dependent group, demand peptide-lipid interactions that can be readilymodulated. This modulation enables movement of peptides within membranes or within thelipid-water interface. These conditions make these peptides especially suitable for NMR studies.

Place, publisher, year, edition, pages
DBB, SU , 2010. , 59 p.
Keyword [en]
peptide-lipid interaction, membrane mimetic, NMR, biophysics
National Category
Biophysics
Research subject
Biophysics
Identifiers
URN: urn:nbn:se:su:diva-59534OAI: oai:DiVA.org:su-59534DiVA: diva2:429221
Presentation
2010-04-22, K205, Arrhenius Laboratories for Natural Sciences, Stockholm, 15:00 (English)
Opponent
Supervisors
Available from: 2012-01-25 Created: 2011-07-04 Last updated: 2012-01-25Bibliographically approved
List of papers
1. Solution structure of the HsapBK K+ channel voltage-sensor paddle sequence
Open this publication in new window or tab >>Solution structure of the HsapBK K+ channel voltage-sensor paddle sequence
2009 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 48, no 25, 5813-5821 p.Article in journal (Refereed) Published
Abstract [en]

Voltage-gated potassium channels open and close in response to changes in the membrane potential. In this study, we have determined the NMR solution structure of the putative S3b-S4 voltage-sensor paddle fragment, the part that moves to mediate voltage gating, of the HsapBK potassium channel in dodecylphosphocholine (DPC) micelles. This paper presents the first structure of the S3b-S4 fragment from a BK channel. Diffusion coefficients as determined from PFG NMR experiments showed that a well-defined complex between the peptide and DPC molecules was formed. The structure reveals a helix-turn-helix motif, which is in agreement with crystal structures of other voltage-gated potassium channels, thus indicating that it is feasible to study the isolated fragment. The paddle motifs generally contain several basic residues, implicated in the gating. The critical Arg residues in this structure all reside on the surface, which is in agreement with crystal structures of K(v) channels. Similarities in the structure of the S3b-S4 fragment in BK and K(v) channels as well as important differences are seen, which may be important for explaining the details in paddle movement within a bilayer.

Keyword
NMR solution structure, S3b−S4 fragment, paddle
National Category
Biophysics
Research subject
Biophysics; Biochemistry
Identifiers
urn:nbn:se:su:diva-31727 (URN)10.1021/bi9004599 (DOI)000267326500006 ()19456106 (PubMedID)
Funder
Swedish Research Council, 621-2011-5964
Available from: 2009-11-25 Created: 2009-11-25 Last updated: 2017-12-12

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