Eliducating the Distinctions between Open-State Monomers and Dimers of Human Tissue Transglutaminase

Abstract

Transglutaminase 2 (TG2) is a pivotal enzyme involved in various biological processes such as wound healing, apoptosis, and cell differentiation. Depending on the environmental conditions, TG2 can adopt two distinct conformations: the open and closed states. Notably, the open conformation of TG2 has been associated with the pathogenesis of several diseases, including celiac disease and certain cancers. Recent investigations have demonstrated that within human cells, open-state TG2 can exist both as monomers and as dimers. The monomeric form primarily exhibits transamidation activity, whereas the dimeric form is postulated to exert cytotoxic effects. While several structures of the monomeric open-state TG2 are available in the Protein Data Bank, structures representing the dimeric form remain elusive. The objective of this study is to elucidate the structural distinctions between TG2 monomers and dimers using small-angle X-ray scattering (SAXS).