Membrane Induced Structure in Transmembrane Signaling Proteins and Peptides: Peptide–Lipid Interactions Studied by Spectroscopic Methods
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Biological membranes, defining the boundary of cells and eukaryotic organelles, are mainly composed of lipids and membrane proteins. Interactions between these lipids and proteins are needed to preserve the tight seal of the membrane, but also to induce structure for proper function in many membrane proteins. In this thesis, interactions between three different kinds of peptides, i.e. small proteins, and model membranes are studied by spectroscopic methods.
First, the membrane interaction of two paddle domains, KvAPp, from the voltage-gated potassium channel KvAP from Aeropyrum pernix, and HsapBKp, from the human, large conductance, calcium-activated potassium channel HsapBK, was studied (paper I and II). In paper I, a high-resolution solution NMR structure of HsapBKp in detergent micelles is presented revealing a helix-turn-helix motif. Small structural differences between HsapBKp and KvAPp, positioning the arginines differently, are presented. These structural differences may explain why BK channels are weakly voltage-gated. In paper II, it is shown that HsapBKp perturbs the membrane more than KvAPp and that the membrane perturbation is related to β-structure and to dynamics in the turn in the helix-turn-helix motif.
Second, the membrane interaction of HAMP domains modulating transmission in prokaryotic transmembrane signaling was studied (paper III). Based on the membrane interaction of the AS1 segments of the HAMP domains, two groups were identified: one strongly membrane interacting and one weakly membrane interacting. The two groups are suggested to use different signaling mechanisms.
Third, nonspecific binding of proinsulin C-peptide, the linker peptide connecting chain A and B in insulin, to model membranes was studied (paper IV). The study revealed that C-peptide binds to a model membrane at low pH, but the membrane induces no large structural rearrangements of the peptide.
Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University , 2012. , 59 p.
peptide-lipid interaction, paddle domain, voltage gating, voltage sensor domain, micelle, phospholipid bicelle, solution structure, HAMP domain, nuclear magnetic resonance spectroscopy, circular dichroism spectroscopy, nonspecific interaction
Research subject Biophysics
IdentifiersURN: urn:nbn:se:su:diva-79051ISBN: 978-91-7447-564-7OAI: oai:DiVA.org:su-79051DiVA: diva2:546714
2012-09-28, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Schnell, Jason, Dr.
Mäler, Lena, Professor
List of papers