LEM domain

LEM domain
Identifiers
SymbolLEM
PfamPF03020
Pfam clanCL0306
InterProIPR003887
SMARTSM00540
PROSITEPS50954
CDDcd12934
Available protein structures:
PDB  IPR003887 PF03020 (ECOD; PDBsum)  
AlphaFold

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]

References

  1. ^ Brachner A, Reipert S, Foisner R, Gotzmann J (December 2005). "LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins". Journal of Cell Science. 118 (Pt 24): 5797–5810. doi:10.1242/jcs.02701. PMID 16339967.
  2. ^ Barton LJ, Soshnev AA, Geyer PK (June 2015). "Networking in the nucleus: a spotlight on LEM-domain proteins". Current Opinion in Cell Biology. 34: 1–8. doi:10.1016/j.ceb.2015.03.005. PMC 4522374. PMID 25863918.
  3. ^ Herrada I, Bourgeois B, Samson C, Buendia B, Worman HJ, Zinn-Justin S (2016). "Purification and Structural Analysis of LEM-Domain Proteins". Intermediate Filament Associated Proteins. Methods in Enzymology. Vol. 569. pp. 43–61. doi:10.1016/bs.mie.2015.07.008. ISBN 978-0-12-803469-9. PMID 26778552.
  4. ^ Cai M, Huang Y, Ghirlando R, Wilson KL, Craigie R, Clore GM (August 2001). "Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA". The EMBO Journal. 20 (16): 4399–4407. doi:10.1093/emboj/20.16.4399. PMC 125263. PMID 11500367.

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