1bjb: Difference between revisions
New page: left|200px<br /> <applet load="1bjb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bjb" /> '''SOLUTION NMR STRUCTURE OF AMYLOID BETA[E16]... |
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'''SOLUTION NMR STRUCTURE OF AMYLOID BETA[E16], RESIDUES 1-28, 14 STRUCTURES'''<br /> | '''SOLUTION NMR STRUCTURE OF AMYLOID BETA[E16], RESIDUES 1-28, 14 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
NMRsolution structures are reported for two mutants (K16E, K16F) of the | NMRsolution structures are reported for two mutants (K16E, K16F) of the soluble amyloid beta peptide Abeta(1-28). The structural effects of these mutations of a positively charged residue to anionic and hydrophobic residues at the alpha-secretase cleavage site (Lys16-Leu17) were examined in the membrane-simulating solvent aqueous SDS micelles. Overall the three-dimensional structures were similar to that for the native Abeta(1-28) sequence in that they contained an unstructured N-terminus and a helical C-terminus. These structural elements are similar to those seen in the corresponding regions of full-length Abeta peptides Abeta(1-40) and Abeta(1-42), showing that the shorter peptides are valid model systems. The K16E mutation, which might be expected to stabilize the macrodipole of the helix, slightly increased the helix length (residues 13-24) relative to the K16F mutation, which shortened the helix to between residues 16 and 24. The observed sequence-dependent control over conformation in this region provides an insight into possible conformational switching roles of mutations in the amyloid precursor protein from which Abeta peptides are derived. In addition, if conformational transitions from helix to random coil to sheet precede aggregation of Abeta peptides in vivo, as they do in vitro, the conformation-inducing effects of mutations at Lys16 may also influence aggregation and fibril formation. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1BJB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1BJB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BJB OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Craik, D | [[Category: Craik, D J.]] | ||
[[Category: Poulsen, S | [[Category: Poulsen, S A.]] | ||
[[Category: Watson, A | [[Category: Watson, A A.]] | ||
[[Category: alzheimer's disease]] | [[Category: alzheimer's disease]] | ||
[[Category: amyloid beta-peptide]] | [[Category: amyloid beta-peptide]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:55:54 2008'' | ||
Revision as of 12:55, 21 February 2008
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SOLUTION NMR STRUCTURE OF AMYLOID BETA[E16], RESIDUES 1-28, 14 STRUCTURES
OverviewOverview
NMRsolution structures are reported for two mutants (K16E, K16F) of the soluble amyloid beta peptide Abeta(1-28). The structural effects of these mutations of a positively charged residue to anionic and hydrophobic residues at the alpha-secretase cleavage site (Lys16-Leu17) were examined in the membrane-simulating solvent aqueous SDS micelles. Overall the three-dimensional structures were similar to that for the native Abeta(1-28) sequence in that they contained an unstructured N-terminus and a helical C-terminus. These structural elements are similar to those seen in the corresponding regions of full-length Abeta peptides Abeta(1-40) and Abeta(1-42), showing that the shorter peptides are valid model systems. The K16E mutation, which might be expected to stabilize the macrodipole of the helix, slightly increased the helix length (residues 13-24) relative to the K16F mutation, which shortened the helix to between residues 16 and 24. The observed sequence-dependent control over conformation in this region provides an insight into possible conformational switching roles of mutations in the amyloid precursor protein from which Abeta peptides are derived. In addition, if conformational transitions from helix to random coil to sheet precede aggregation of Abeta peptides in vivo, as they do in vitro, the conformation-inducing effects of mutations at Lys16 may also influence aggregation and fibril formation.
DiseaseDisease
Known diseases associated with this structure: Alzheimer disease-1, APP-related OMIM:[104760], Amyloidosis, cerebroarterial, Dutch type OMIM:[104760], Amyloidosis, cerebroarterial, Iowa type OMIM:[104760], Blood group, P system OMIM:[607922]
About this StructureAbout this Structure
1BJB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structures in aqueous SDS micelles of two amyloid beta peptides of A beta(1-28) mutated at the alpha-secretase cleavage site (K16E, K16F)., Poulsen SA, Watson AA, Fairlie DP, Craik DJ, J Struct Biol. 2000 Jun;130(2-3):142-52. PMID:10940222
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