2XKU: Prion-like conversion during amyloid formation at atomic resolution

Numerous studies of amyloid assembly have indicated that partially folded protein species are responsible for initiating aggregation. Despite their importance, the structural and dynamic features of amyloidogenic intermediates and the molecular details of how they cause aggregation remain elusive. Here, we use DeltaN6, a truncation variant of the naturally amyloidogenic protein beta(2)-microglobulin (beta(2)m), to determine the solution structure of a nonnative amyloidogenic intermediate at high resolution. The structure of DeltaN6 reveals a major repacking of the hydrophobic core to accommodate the nonnative peptidyl-prolyl trans-isomer at Pro32. These structural changes, together with a concomitant pH-dependent enhancement in backbone dynamics on a microsecond-millisecond timescale, give rise to a rare conformer with increased amyloidogenic potential. We further reveal that catalytic amounts of DeltaN6 are competent to convert nonamyloidogenic human wild-type beta(2)m (Hbeta(2)m) into a rare amyloidogenic conformation and provide structural evidence for the mechanism by which this conformational conversion occurs.
PDB ID: 2XKUDownload
MMDB ID: 88432
PDB Deposition Date: 2010/7/12
Updated in MMDB: 2018/05
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2XKU: monomeric; determined by author
Molecular Components in 2XKU
Label Count Molecule
Protein (1 molecule)
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB