2otk: Difference between revisions

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[[Image:2otk.jpg|left|200px]]
{{Seed}}
[[Image:2otk.png|left|200px]]


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{{STRUCTURE_2otk|  PDB=2otk  |  SCENE=  }}  
{{STRUCTURE_2otk|  PDB=2otk  |  SCENE=  }}  


'''Structure of Alzheimer Ab peptide in complex with an engineered binding protein'''
===Structure of Alzheimer Ab peptide in complex with an engineered binding protein===




==Overview==
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According to the amyloid hypothesis, the pathogenesis of Alzheimer's disease is triggered by the oligomerization and aggregation of the amyloid-beta (Abeta) peptide into protein plaques. Formation of the potentially toxic oligomeric and fibrillar Abeta assemblies is accompanied by a conformational change toward a high content of beta-structure. Here, we report the solution structure of Abeta(1-40) in complex with the phage-display selected affibody protein Z(Abeta3), a binding protein of nanomolar affinity. Bound Abeta(1-40) features a beta-hairpin comprising residues 17-36, providing the first high-resolution structure of Abeta in beta conformation. The positions of the secondary structure elements strongly resemble those observed for fibrillar Abeta. Z(Abeta3) stabilizes the beta-sheet by extending it intermolecularly and by burying both of the mostly nonpolar faces of the Abeta hairpin within a large hydrophobic tunnel-like cavity. Consequently, Z(Abeta3) acts as a stoichiometric inhibitor of Abeta fibrillation. The selected Abeta conformation allows us to suggest a structural mechanism for amyloid formation based on soluble oligomeric hairpin intermediates.
The line below this paragraph, {{ABSTRACT_PUBMED_18375754}}, adds the Publication Abstract to the page
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{{ABSTRACT_PUBMED_18375754}}


==About this Structure==
==About this Structure==
2OTK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Engineered_binding_protein Engineered binding protein]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OTK OCA].  
2OTK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Engineered_binding_protein Engineered binding protein]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OTK OCA].  


==Reference==
==Reference==
Stabilization of a beta-hairpin in monomeric Alzheimer's amyloid-beta peptide inhibits amyloid formation., Hoyer W, Gronwall C, Jonsson A, Stahl S, Hard T, Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5099-104. Epub 2008 Mar 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18375754 18375754]
Stabilization of a beta-hairpin in monomeric Alzheimer's amyloid-beta peptide inhibits amyloid formation., Hoyer W, Gronwall C, Jonsson A, Stahl S, Hard T, Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5099-104. Epub 2008 Mar 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18375754 18375754]
Selection and characterization of Affibody ligands binding to Alzheimer amyloid beta peptides., Gronwall C, Jonsson A, Lindstrom S, Gunneriusson E, Stahl S, Herne N, J Biotechnol. 2007 Jan 30;128(1):162-83. Epub 2006 Sep 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17088007 17088007]
[[Category: Engineered binding protein]]
[[Category: Engineered binding protein]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Peptide binding protein]]
[[Category: Peptide binding protein]]
[[Category: Protein-peptide complex]]
[[Category: Protein-peptide complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:26:03 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:09:04 2008''
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