1bjb
SOLUTION NMR STRUCTURE OF AMYLOID BETA[E16], RESIDUES 1-28, 14 STRUCTURES
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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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