1qcm

From Proteopedia

Revision as of 14:44, 15 February 2008

AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES

Overview

The three-dimensional structure of amyloid beta peptide (25-35), which has, neurotoxic activity, in lithium dodecyl sulfate micelles was determined by, two-dimensional 1H NMR spectroscopy with simulated annealing calculations., A total of 20 converged amyloid beta peptide structures were obtained on, the basis of 110 experimental constraints, including 106 distance, constraints reduced from the nuclear Overhauser effect (NOE), connectivities and four torsion angle (phi) constraints. The atomic root, mean square difference about averaged coordinates is 1.04 +/- 0.25 A for, the backbone atoms (N, C alpha, C) and 1.39 +/- 0.27 A for all heavy atoms, of the entire peptide. The molecular structure of amyloid beta peptide in, membrane-mimicking environment is composed of a short alpha helix in the C, terminal position. The three residues from the N-terminus are disordered, but the remaining eight C-terminal residues are well-ordered, which is, supported by the RMSD values of the C-terminal region, Lys28-Leu34. In, this region, the RMS differences from averaged coordinates are 0.26 +/-, 0.11 A for the backbone atoms (N, C alpha, C) and 0.77 +/- 0.21 A for all, heavy atoms, which is very low compared with those for the entire peptide., The four amino acid residues from the N-terminus are hydrophilic and the, other seven amino acid residues in C-terminus are hydrophobic. So, our, results show that the C-terminal region of amyloid beta peptide (25-35) is, buried in the membrane and assumes alpha-helical structure, whereas the, N-terminal region is exposed to the solvent with a flexible structure., This structure is very similar to membrane-mediated structure of substance, P previously reported. The three-dimensional structure of a non-neurotoxic, mutant of amyloid beta peptide (25-35), where Asn27 is replaced by Ala, in, lithium dodecyl sulfate micelles was also determined. The structure is, similar to that of the wild type amyloid beta peptide (25-35) in the, C-terminal region, but the N-terminal flexible region is different. The, structural comparison of amyloid beta peptide (25-35), its non-neurotoxic, mutant and substance P gives a structural basis to understand the, mechanism of neurotoxicity caused by amyloid beta peptide.

Disease

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 Structure

1QCM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment., Kohno T, Kobayashi K, Maeda T, Sato K, Takashima A, Biochemistry. 1996 Dec 17;35(50):16094-104. PMID:8973180

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