| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Bokvist, Marcus, et al.
(författare)
-
Two Types of Alzheimer’s β-Amyloid (1–40) Peptide Membrane Interactions : Aggregation Preventing Transmembrane Anchoring Versus Accelerated Surface Fibril Formation
- 2004
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 335:4, s. 1039-1049
-
Tidskriftsartikel (refereegranskat)abstract
- The 39–42 amino acid long, amphipathic amyloid-β peptide (Aβ) is one of the key components involved in Alzheimer's disease (AD). In the neuropathology of AD, Aβ presumably exerts its neurotoxic action via interactions with neuronal membranes. In our studies a combination of 31P MAS NMR (magic angle spinning nuclear magnetic resonance) and CD (circular dichroism) spectroscopy suggest fundamental differences in the functional organization of supramolecular Aβ1–40 membrane assemblies for two different scenarios with potential implication in AD: Aβ peptide can either be firmly anchored in a membrane upon proteolytic cleavage, thereby being prevented against release and aggregation, or it can have fundamentally adverse effects when bound to membrane surfaces by undergoing accelerated aggregation, causing neuronal apoptotic cell death. Acidic lipids can prevent release of membrane inserted Aβ1–40 by stabilizing its hydrophobic transmembrane C-terminal part (residue 29–40) in an α-helical conformation via an electrostatic anchor between its basic Lys28 residue and the negatively charged membrane interface. However, if Aβ1–40 is released as a soluble monomer, charged membranes act as two-dimensional aggregation-templates where an increasing amount of charged lipids (possible pathological degradation products) causes a dramatic accumulation of surface-associated Aβ1–40 peptide followed by accelerated aggregation into toxic structures. These results suggest that two different molecular mechanisms of peptide–membrane assemblies are involved in Aβ′s pathophysiology with the finely balanced type of Aβ–lipid interactions against release of Aβ from neuronal membranes being overcompensated by an Aβ–membrane assembly which causes toxic β-structured aggregates in AD. Therefore, pathological interactions of Aβ peptide with neuronal membranes might not only depend on the oligomerization state of the peptide, but also the type and nature of the supramolecular Aβ–membrane assemblies inherited from Aβ′s origin.
|
|
| 5. |
- Bonev, Boyan, et al.
(författare)
-
Electrostatic peptide-lipid interactions of amyloid-β peptide and pentalysine with membrane surfaces monitored by 31P MAS NMR
- 2001
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 3:14, s. 2904-2910
-
Tidskriftsartikel (refereegranskat)abstract
- High-resolution 31P magic angle spinning (MAS) NMR spectroscopy is presented as a direct and non-perturbing method for measuring changes in surface charge density occurring in mixed phospholipid membranes upon binding of charged surface-active peptides. 31P MAS NMR was used to investigate mixed lipid membranes of neutral phosphatidylcholine and negatively charged phosphatidylglycerol where the molar fraction of the charged lipid was varied from 0 to 1. The chemical shifts of the individual membrane lipids showed a simple variation in response to changes in the fraction of the negatively charged component phosphatidylglycerol. Addition of the positively charged amyloid-β1-40 peptide, a key substance in Alzheimer's disease, resulted in changes in the isotropic chemical shifts of the membrane lipid phosphates in a way consistent with reduction in the negative surface charge of the mixed lipid bilayers. Binding of different amounts of the positively charged peptide pentalysine to L-α-dioleoylphosphatidylcholine/L-α-dioleoylphosphatidylglycerol(DOPC/DOPG) vesicles (2 : 1 molar ratio) also showed a systematic variation of both chemical shift values. These changes were described by a simple two-site model and indicate purely electrostatic binding of pentalysine.
|
|
| 6. |
- Byström, Tomas, et al.
(författare)
-
Orientation of a polyleucine-based peptide in phosphatidylcholine bilayers of different thickness. Solid-state NMR and CD spectroscopy
- 2003
-
Ingår i: Colloids and Surfaces A: Physicochemical and Engineering Aspects. ; 228:1-3, s. 37-42
-
Tidskriftsartikel (refereegranskat)abstract
- A study was performed of the orientation and secondary structure of the peptide pLeuD11 (KKGL7DL[15N]WL9KKA) in phosphatidylcholine (PC) bilayers. The lipid bilayer thickness was varied by using PCs with monounsaturated acyl chains of different lengths, ranging from 14 to 24 carbon atoms. The peptide/lipid molar ratio was kept at 1:30 for all systems with water content of 50 wt.%. The secondary structure was determined by circular dichroism (CD) spectroscopy. The peptide adopted a transmembrane orientation in all bilayers, independent on their thickness. The location of the peptide was determined by 15N solid-state magic angle spinning (MAS) NMR spectroscopy, exploiting the effects of paramagnetic lanthanide ions at the membrane surface. From static solid-state 31P NMR spectroscopy measurements it was concluded that all lipid/peptide systems formed a lamellar liquid crystalline phase. As found by CD the distribution of secondary structures in the peptide changed only slightly for the different lipid membranes. The fraction of -helix was highest (≈60%) in bilayers with lipids, having an acyl chain length of 18 and 22 carbon atoms, while for lipids with 14 and 24 carbon atoms the helical content decreased slightly to about 50%. This reduction was accompanied by an increase in the fraction of β-like structures.
|
|
| 7. |
- Gröbner, Gerhard, et al.
(författare)
-
Light triggered activation of the G-protein coupled photoreceptor rhodopsin: A structural and functional description
- 2000
-
Ingår i: Recent research developments in bioenergetics. ; 1, s. 103-15
-
Tidskriftsartikel (refereegranskat)abstract
- Rhodopsin, a 39 kDa photoreceptor is responsible for converting an incident photon of visible light into an optic nerve impulse. The protein belongs to the family of G-protein coupled receptors, which transduce chemical or optical signals across a cellular membrane. The ability of rhodopsin to convert light energy into a neuronal response is the result of isomerization of its chromophore retinal during the early primary photochemical events leading to activation of the protein. This activation is initiated by the photoisomerization of 11-cis retinal which is covalently attached to Lys-296 as a protonated Schiff base and gets slowly released from the protein as all-trans retinal. In order to understand the mechanism of conversion of light energy via this receptor protein into a final neuronal impulse, a precise elucidation of the structural organization of the chromophore binding site in the photoreceptor and its interaction with the chromophore after visual excitation is essential. Recently, various solid state NMR studies using nonperturbing spin reporters have provided an atomic level description of the overall orientation and structure of the chromophore within the binding pocket for various stages of the photoactivation, well ahead of any crystallographic efforts.
|
|
| 8. |
- Gröbner, Gerhard, et al.
(författare)
-
Observations of light-induced structural changes of retinal within rhodopsin
- 2000
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 405, s. 810-3
-
Tidskriftsartikel (refereegranskat)abstract
- Photo-isomerization of the 11-cis retinal chromophore activates the mammalian light-receptor rhodopsin1, a representative member of a major superfamily of transmembrane G-protein-coupled receptor proteins (GPCRs) responsible for many cell signal communication pathways. Although low-resolution (5 Å) electron microscopy studies2, 3 confirm a seven transmembrane helix bundle as a principal structural component of rhodopsin, the structure of the retinal within this helical bundle is not known in detail. Such information is essential for any theoretical or functional understanding of one of the fastest occurring photoactivation processes in nature, as well as the general mechanism behind GPCR activation4, 5, 6. Here we determine the three-dimensional structure of 11-cis retinal bound to bovine rhodopsin in the ground state at atomic level using a new high-resolution solid-state NMR method7. Significant structural changes are observed in the retinal following activation by light to the photo-activated MI state of rhodopsin giving the all-trans isomer of the chromophore. These changes are linked directly to the activation of the receptor, providing an insight into the activation mechanism of this class of receptors at a molecular level.
|
|
| 9. |
|
|
| 10. |
|
|
