PDBsum entry 3hyd

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Protein fibril PDB id
Waters ×3
PDB id:
Name: Protein fibril
Title: Lvealyl peptide derived from human insulin chain b, residues 11-17
Structure: Insulin. Chain: a. Fragment: unp residues 34-41 of chain b. Synonym: insulin b chain. Engineered: yes
Source: Synthetic: yes
1.00Å     R-factor:   0.149     R-free:   0.180
Authors: M.I.Ivanova,M.R.Sawaya,D.Eisenberg
Key ref:
M.I.Ivanova et al. (2009). Molecular basis for insulin fibril assembly. Proc Natl Acad Sci U S A, 106, 18990-18995. PubMed id: 19864624 DOI: 10.1073/pnas.0910080106
22-Jun-09     Release date:   06-Oct-09    


DOI no: 10.1073/pnas.0910080106 Proc Natl Acad Sci U S A 106:18990-18995 (2009)
PubMed id: 19864624  
Molecular basis for insulin fibril assembly.
M.I.Ivanova, S.A.Sievers, M.R.Sawaya, J.S.Wall, D.Eisenberg.
In the rare medical condition termed injection amyloidosis, extracellular fibrils of insulin are observed. We found that the segment of the insulin B-chain with sequence LVEALYL is the smallest segment that both nucleates and inhibits the fibrillation of full-length insulin in a molar ratio-dependent manner, suggesting that this segment is central to the cross-beta spine of the insulin fibril. In isolation from the rest of the protein, LVEALYL forms microcrystalline aggregates with fibrillar morphology, the structure of which we determined to 1 A resolution. The LVEALYL segments are stacked into pairs of tightly interdigitated beta-sheets, each pair displaying the dry steric zipper interface typical of amyloid-like fibrils. This structure leads to a model for fibrils of human insulin consistent with electron microscopic, x-ray fiber diffraction, and biochemical studies.
  Selected figure(s)  
Figure 3.
Atomic structure of B-chain segment LVEALYL, which forms fibril-like microcrystals. (A) View perpendicular to fibril axis showing pair of β-sheets formed by LVEALYL molecules. Crystal needle length runs vertical in this orientation. (B) View down fibril axis showing one layer of interdigitated pair of LVEALYL molecules, which interlock tightly to form the dry steric zipper interface. Pairs of extended β-strands of LVEALYL are stacked in register upon each other, so this figure may be thought of as a projection of two β-sheets, each containing some 100,000 layers. Note that this dry steric zipper interface is devoid of water molecules (shown in yellow). (C) Packing of LVEALYL molecules in crystal, viewed down fibril axis as in (B). Molecules forming the dry steric zipper interface are purple and are separated by water molecules from the next sheets in gray. Thus in LVEALYL crystals one side of each sheet faces water molecules (wet interface).
Figure 5.
Fibril model of insulin. (Left) Native structure of the insulin dimer (PDB code 1GUJ). A and B chains of insulin molecule are shown in pale red and pale blue, respectively. The LVEALYL segment, which forms the spine of the fibril, is in dark blue. The SLYQLENY segment, from the A chain, which forms auxiliary sheets to the spine of the fibril, is in dark red. Disulfide bonds are shown in yellow. (Middle) View down fibril axis of four β-sheets of crystal structure of B chain LVEALYL. The two sheets forming the dry steric zipper interface are in blue. Water molecules are shown as green spheres. (Right) View of fibril model, looking down fibril axis. One layer of fibril model is made by stretching both monomers of native insulin (left) in a horizontal direction, converting the deep blue helix of the B chain and the deep red helix of the A chain into extended β-strands. These extended β-strands are given the conformations of the four chain segments of the crystal structure shown in the middle. Thus the spine of the fibril consists of a dry steric zipper formed by the mating of the central two LVEALYL strands from the B chains of the two insulin molecules, plus two outer strands from the A chains of the two molecules.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20941707 C.L.Heldt, S.Zhang, and G.Belfort (2011).
Asymmetric amyloid fibril elongation: a new perspective on a symmetric world.
  Proteins, 79, 92-98.  
20632994 A.Noormägi, J.Gavrilova, J.Smirnova, V.Tõugu, and P.Palumaa (2010).
Zn(II) ions co-secreted with insulin suppress inherent amyloidogenic properties of monomeric insulin.
  Biochem J, 430, 511-518.  
20685658 M.I.Apostol, M.R.Sawaya, D.Cascio, and D.Eisenberg (2010).
Crystallographic studies of prion protein (PrP) segments suggest how structural changes encoded by polymorphism at residue 129 modulate susceptibility to human prion disease.
  J Biol Chem, 285, 29671-29675.
PDB codes: 3nhc 3nhd
20979077 R.Giraldo (2010).
Amyloid assemblies: protein legos at a crossroads in bottom-up synthetic biology.
  Chembiochem, 11, 2347-2357.  
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