LEM domain

Last updated

LEM domain
Identifiers
SymbolLEM
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. [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.