PDBsum entry 2e8d

Protein fibril, immune system

PDB id: 2e8d

Contents

Protein chains

22 a.a.

PDB id:

2e8d

Name:

Protein fibril, immune system

Title:

3d structure of amyloid protofilaments of beta2-microglobulin fragment probed by solid-state nmr

Structure:

Beta-2-microglobulin. Chain: a, b, c, d. Fragment: residues 40-61 (in uniprot numbering). Synonym: k3 peptide of beta2-microglobulin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: b2m. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

10 models

Authors:

T.Fujiwara

Key ref:

K.Iwata et al. (2006). 3D structure of amyloid protofilaments of beta2-microglobulin fragment probed by solid-state NMR. Proc Natl Acad Sci U S A, 103, 18119-18124. PubMed id: 17108084 DOI: 10.1073/pnas.0607180103

Date:

19-Jan-07 Release date: 13-Feb-07

Protein chains

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 22 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.0607180103

Proc Natl Acad Sci U S A 103:18119-18124 (2006)

PubMed id: 17108084

3D structure of amyloid protofilaments of beta2-microglobulin fragment probed by solid-state NMR.

K.Iwata, T.Fujiwara, Y.Matsuki, H.Akutsu, S.Takahashi, H.Naiki, Y.Goto.

ABSTRACT

Understanding the structure and formation of amyloid fibrils, the filamentous aggregates of proteins and peptides, is crucial in preventing diseases caused by their deposition and, moreover, for obtaining further insight into the mechanism of protein folding and misfolding. We have combined solid-state NMR, x-ray fiber diffraction, and atomic force microscopy to reveal the 3D structure of amyloid protofilament-like fibrils formed by a 22-residue K3 peptide (Ser(20)-Lys(41)) of beta(2)-microglobulin, a protein responsible for dialysis-related amyloidosis. Although a uniformly (13)C,(15)N-labeled sample was used for the NMR measurements, we could obtain the 3D structure of the fibrils on the basis of a large number of structural constraints. The conformation of K3 fibrils was found to be a beta-strand-loop-beta-strand with each K3 molecule stacked in a parallel and staggered manner. It is suggested that the fibrillar conformation is stabilized by intermolecular interactions, rather than by intramolecular hydrophobic packing as seen in globular proteins. Together with thermodynamic studies of the full-length protein, formation of the fibrils is likely to require side chains on the intermolecular surface to pack tightly against those of adjacent monomers. By revealing the structure of beta(2)-microglobulin protofilament-like fibrils, this work represents technical progress in analyzing amyloid fibrils in general through solid-state NMR.

Selected figure(s)

Figure 1.
Fig. 1. AFM images and x-ray fiber diffraction of K3 fibrils. (A) AFM images of K3 fibrils formed in 20% (vol/vol) TFE/10 mM HCl. The scan was performed with a 25-fold diluted sample on a freshly cleaved mica surface. The white scale bar represents 500 nm, and the scan size is 2.5 x 2.5 µm with 512 x 512 points. (B) X-ray fiber diffraction of the K3 fibrils with incident beam perpendicular to the fibril axis. The data shows a typical cross- pattern. The diffractions corresponding to 4.72 Å (red) and 9.52 Å (blue) indicate the distance between -strands in the -sheet and -sheet layers in the laminated structure, respectively.

Figure 5.
Fig. 5. 3D structures of tetrameric K3 and monomeric K3 in the fibrillar state. The conformation of K3 in the fibrillar state obtained by simulated annealing molecular dynamics by using CNS. (A) Calculated ensemble of tetrameric structures of K3 fibrils. (B) Ribbon model representation of tetrameric K3 in parallel STAG(+1) conformation. (C) The conformation of one K3 structure in the fibrillar state. (D) Comparison of the conformation of the K3 region in the crystal structure of native 2-m. Notably, the residues between Phe^22 and Ser^28 are flipped relative to the crystal structure of native 2-m in the fibrillar state.

Figures were selected by an automated process.