Stacked sets of parallel, in-register beta-strands of beta2-microglobulin in amyloid fibrils revealed by site-directed spin labeling and chemical labeling.

ABSTRACT: beta(2)-microglobulin (beta(2)m) is a 99-residue protein with an immunoglobulin fold that forms beta-sheet-rich amyloid fibrils in dialysis-related amyloidosis. Here the environment and accessibility of side chains within amyloid fibrils formed in vitro from beta(2)m with a long straight morphology are probed by site-directed spin labeling and accessibility to modification with N-ethyl maleimide using 19 site-specific cysteine variants. Continuous wave electron paramagnetic resonance spectroscopy of these fibrils reveals a core predominantly organized in a parallel, in-register arrangement, by contrast with other beta(2)m aggregates. A continuous array of parallel, in-register beta-strands involving most of the polypeptide sequence is inconsistent with the cryoelectron microscopy structure

SUBMITTER: Ladner CL 

PROVIDER: S-EPMC2878032 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature