LEM domain

The LEM domain is a conserved protein motif present in multiple inner nuclear membrane proteins that play roles in nuclear structure and function. This approximately 40-amino acid region enables proteins to bind the barrier-to-autointegration factor (BAF), tethering repressive chromatin and regulating genome organization at the nuclear periphery. LEM domain-containing proteins are important for nuclear envelope integrity, chromatin architecture, and gene expression control, with disruptions implicated in diverse human diseases known as laminopathies.^[1][2]

The LEM domain is a compact approximately 50-residue alpha-helical module that adopts a characteristic three-helix bundle fold, typically described as a short N-terminal helical turn followed by two longer, roughly parallel α helices connected by an 11–12 residue loop. This fold is shared with structurally related SAP and HeH domains, forming a conserved scaffold whose exposed residues on helix 1, the N-terminus of helix 2, and the inter-helical loop create the interaction surface for binding partners such as BAF, DNA, or other macromolecules, depending on the specific surface charge and hydrophobic patterning.^[3][4]