LEM domain

LEM domain
Identifiers
Symbol	LEM
Pfam	PF03020
Pfam clan	CL0306
InterPro	IPR003887
SMART	SM00540
PROSITE	PS50954
CDD	cd12934
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.

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.