Sandbox k11v
From Proteopedia
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== Introduction == | == Introduction == | ||
| - | Amyloid fibrils were first assumed to be the agents of Amyloid diseases,including Alzheimer’s,Parkinson’s and the prion conditions.But studies from many laboratories suggest that the reason for this disorder are lower molecular weight entities known as small amyloid oligomers,instead of the associated protein fibrils.Segment of amyloid forming protein <scene name='77/771966/3l1g_full_structure/1'>alpha-beta crystallin</scene> makes oligomeric complex which exhibits properties of other amyloid oligomers.They are rich in beta-sheet structure and these oligomer can be identified by a conformational antibody(A11) that binds oligomers but not fibrils,irrespective of sequence of constituent protein.This protein is a chaperone that forms amyloid fibrils.The structure of oligomer shows a cylindrical barrel,made up of six anti-parallel protein strands known as cylindrin.This segment(coloured in black) termed as <scene name='77/771966/K11v_in_black/1'>K11V</scene> forms the cylindrin structure. | + | Amyloid fibrils were first assumed to be the agents of Amyloid diseases,including Alzheimer’s,Parkinson’s and the prion conditions.But studies from many laboratories suggest that the reason for this disorder are lower molecular weight entities known as small amyloid oligomers,instead of the associated protein fibrils.Segment of amyloid forming protein <scene name='77/771966/3l1g_full_structure/1'>alpha-beta crystallin(ABC)</scene> makes oligomeric complex which exhibits properties of other amyloid oligomers.They are rich in beta-sheet structure and these oligomer can be identified by a conformational antibody(A11) that binds oligomers but not fibrils,irrespective of sequence of constituent protein.This protein is a chaperone that forms amyloid fibrils.The structure of oligomer shows a cylindrical barrel,made up of six anti-parallel protein strands known as cylindrin.This segment(coloured in black) termed as <scene name='77/771966/K11v_in_black/1'>K11V</scene> forms the cylindrin structure. |
== Molecular Tour == | == Molecular Tour == | ||
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[[Image:Rosetta_image.jpg | thumb | 300px | right | Ribbon diagram of a single subunit of ABC (16), colored by propensity to form amyloid, with red being the highest and blue the lowest propensity. The segment from residue 90 to 100, termed K11V, forms the cylindrin. ]] | [[Image:Rosetta_image.jpg | thumb | 300px | right | Ribbon diagram of a single subunit of ABC (16), colored by propensity to form amyloid, with red being the highest and blue the lowest propensity. The segment from residue 90 to 100, termed K11V, forms the cylindrin. ]] | ||
| - | The entire 11-residue segment KVKVLGDVIEV forms a <scene name='77/771966/K11v_in_black/1'>hairpin loop</scene> in the 3D structure of ABC.The six residue segment GDVIEV ,termed <scene name='77/771966/Gdviev_black/1'>G6V</scene>,forms fibrils and microcrystals. | + | The entire 11-residue segment KVKVLGDVIEV forms a <scene name='77/771966/K11v_in_black/1'>hairpin loop</scene> in the 3D structure of ABC.The six residue segment GDVIEV ,termed <scene name='77/771966/Gdviev_black/1'>G6V</scene>,forms fibrils and microcrystals.The microcrystals enabled us to determine the atomic structure of G6V, which proved to be a standard class 2 steric zipper, essentially an amyloid-like protofilament. |
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| + | Amyloid fibrils and oligomer are both formed by the hairpin segment KVKVLGDVIEV.K11V forms fibrils similar to those of protein(ABC) on shaking at elevated temperature and also similar to K11V^V2L(K11V-TR).The fibrils diameter range from 20 to 100 nm in electrom microscope.G6V,K11V,K11V-TR are all convertible to amyloid state,as is their parent protein ABC. | ||
[[Image:Table_abc_first_ok.jpg | thumb | 400px | centre | Information about amyloid related oligomers,derived from ABC ]] | [[Image:Table_abc_first_ok.jpg | thumb | 400px | centre | Information about amyloid related oligomers,derived from ABC ]] | ||
Revision as of 13:56, 9 November 2017
Toxic Amyloid Small Oligomer’s atomic view
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References
- ↑ Laganowsky A, Liu C, Sawaya MR, Whitelegge JP, Park J, Zhao M, Pensalfini A, Soriaga AB, Landau M, Teng PK, Cascio D, Glabe C, Eisenberg D. Atomic view of a toxic amyloid small oligomer. Science. 2012 Mar 9;335(6073):1228-31. PMID:22403391 doi:10.1126/science.1213151
