Annexin A11 (ANX11) is a calcium- and lipid-binding protein linked to neurodegenerative diseases through its interaction with the RNA-binding protein TDP-43 (1). These interactions, mediated by low-complexity regions (LCRs), promote the formation of heterotypic amyloid assemblies (2). While the prion-like domain of TDP-43 has been extensively characterized (3), the structural and conformational features of ANX11 remain poorly understood.
We present our ongoing investiations on the interaction between TDP-43 and a series of ANX11 constructs comprising its LCD and flanking regions. Using biophysical and biochemical approaches, we analyze the conformational ensemble of the ANX11 N-terminal constructs with and without the C-terminal domain (CTD) of TDP-43, examining how these interactions modulate self- and co-assembly.
This research aims at shedding light on the conformational determinants driving ANX11–TDP-43 association, providing insight into how these interactions may contribute to heteromeric assemblies implicated in disease.