2X89: Structure Of The Beta2_microglobulin Involved In Amyloidogenesis

Citation:
Abstract
Atomic-level structural investigation of the key conformational intermediates of amyloidogenesis remains a challenge. Here we demonstrate the utility of nanobodies to trap and characterize intermediates of beta2-microglobulin (beta2m) amyloidogenesis by X-ray crystallography. For this purpose, we selected five single domain antibodies that block the fibrillogenesis of a proteolytic amyloidogenic fragment of beta2m (DeltaN6beta2m). The crystal structure of DeltaN6beta2m in complex with one of these nanobodies (Nb24) identifies domain swapping as a plausible mechanism of self-association of this amyloidogenic protein. In the swapped dimer, two extended hinge loops--corresponding to the heptapetide NHVTLSQ that forms amyloid in isolation--are unmasked and fold into a new two-stranded antiparallel beta-sheet. The beta-strands of this sheet are prone to self-associate and stack perpendicular to the direction of the strands to build large intermolecular beta-sheets that run parallel to the axis of growing oligomers, providing an elongation mechanism by self-templated growth.
PDB ID: 2X89Download
MMDB ID: 87964
PDB Deposition Date: 2010/3/7
Updated in MMDB: 2013/09
Experimental Method:
x-ray diffraction
Resolution: 2.16  Å
Source Organism:
Camelus dromedarius
Similar Structures:
Biological Unit for 2X89: dimeric; determined by author and by software (PISA)
Molecular Components in 2X89
Label Count Molecule
Proteins (2 molecules)
2
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.