Transglutaminase catalyzes differential crosslinking of small heat shock proteins and amyloid-beta

Crosslinking of proteins by tissue transglutaminase (tTG) is enhanced in amyloid (Abeta) deposits characteristic of Alzheimer's disease and sporadic inclusion body myositis. Small heat shock proteins (sHsps) also occur in amyloid deposits. We here report the substrate characteristics for tTG of six sHsps. Hsp27, Hsp20 and HspB8 are both lysine- and glutamine-donors, alphaB-crystallin only is a lysine-donor, HspB2 a glutamine-donor, and HspB3 no substrate at all. Close interaction of proteins stimulates crosslinking efficiency as crosslinking between different sHsps only takes place within the same heteromeric complex. We also observed that alphaB-crystallin, Hsp27 and Hsp20 associate with Abeta in vitro, and can be readily crosslinked by tTG.