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BRICHOS Domains Eff...
BRICHOS Domains Efficiently Delay Fibrillation of Amyloid beta-Peptide
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- Willander, Hanna (författare)
- Karolinska Institutet,Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Karolinska Institute
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- Presto, Jenny (författare)
- Karolinska Institutet,Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Karolinska Institute,Department of Anatomy, Physiology, and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, 751 23 Uppsala,
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- Askarieh, Glareh (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylärbiologi,Department of Molecular Biology
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- Biverstål, Henrik (författare)
- Karolinska Institutet
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- Frohm, Birgitta (författare)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Knight, Stefan D. (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylärbiologi,Department of Molecular Biology,Department of Molecular Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences, Biomedical Centre, P. O. Box 590, SE-751 24 Uppsala
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- Johansson, Jan (författare)
- Karolinska Institutet,Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Department of Anatomy, Physiology, and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, 751 23 Uppsala,
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- Linse, Sara (författare)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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(creator_code:org_t)
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- 2012
- 2012
- Engelska.
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:37, s. 31608-31617
- Relaterad länk:
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://res.slu.se/i...
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Abstract
Ämnesord
Stäng
- Amyloid diseases such as Alzheimer, Parkinson, and prion diseases are associated with a specific form of protein mis-folding and aggregation into oligomers and fibrils rich in beta-sheet structure. The BRICHOS domain consisting of similar to 100 residues is found in membrane proteins associated with degenerative and proliferative disease, including lung fibrosis (surfactant protein C precursor; pro-SP-C) and familial dementia (Bri2). We find that recombinant BRICHOS domains from Bri2 and pro-SP-C prevent fibril formation of amyloid beta-peptides (A beta(40) and A beta(42)) far below the stoichiometric ratio. Kinetic experiments show that a main effect of BRICHOS is to prolong the lag time in a concentration-dependent, quantitative, and reproducible manner. An ongoing aggregation process is retarded if BRICHOS is added at any time during the lag phase, but it is too late to interfere at the end of the process. Results from circular dichroism and NMR spectroscopy, as well as analytical size exclusion chromatography, imply that A beta is maintained as an unstructured monomer during the extended lag phase in the presence of BRICHOS. Electron microscopy shows that although the process is delayed, typical amyloid fibrils are eventually formed also when BRICHOS is present. Structural BRICHOS models display a conserved array of tyrosine rings on a five-stranded beta-sheet, with inter-hydroxyl distances suited for hydrogen-bonding peptides in an extended beta-conformation. Our data imply that the inhibitory mechanism is reliant on BRICHOS interfering with molecular events during the lag phase.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomaterials Science (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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