The interactive Molecular Tour below assumes that you are familiar with the journal article[1].
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 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 forms the cylindrin structure.
Molecular Tour
Oligomer forming segment of ABC were identified by inspection of its 3D structure and by applying the Rosetta-Profile algorithm to its sequence.Two segments of high amyloidogenic propensity,with sequences KVKVLG and GDVIEV (where D indicates Asp; E, Glu; G, Gly; I, Ile; K, Lys; and V, Val).
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 in the 3D structure of ABC.The six residue segment GDVIEV ,termed ,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.
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.
Information about amyloid related oligomers,derived from ABC
PDB'S are
K11V (), K11V-Br2 (), K11V-Br8 (), K11VV2L (), K11V-TR (), and GDVIEV ().
Relevance
Notes & Reference
