1GJJ

N-TERMINAL CONSTANT REGION OF THE NUCLEAR ENVELOPE PROTEIN LAP2

Summary for 1GJJ

• Entry DOI: 10.2210/pdb1gjj/pdb
• Descriptor: LAP2 (1 entity in total)
• Functional Keywords: inner nuclear membrane protein, lamin-associated polypeptide, lem domain, multidimensional nmr dipolar couplings, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 18407.68

Authors

Clore, G.M.,Cai, M. (deposition date: 2001-06-25, release date: 2003-06-24, Last modification date: 2023-12-27)

Primary citation

Cai, M.,Huang, Y.,Ghirlando, R.,Wilson, K.L.,Craigie, R.,Clore, G.M.
Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA.
Embo J., 20:4399-4407, 2001

PubMed Abstract: The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved approximately 40-residue 'LEM' motif. Loss of emerin causes Emery-Dreifuss muscular dystrophy. We have solved the solution NMR structure of the constant region of human LAP2 (residues 1-168). Human LAP2(1-168) has two structurally independent, non-interacting domains located at residues 1-50 ('LAP2-N') and residues 111-152 (LEM-domain), connected by an approximately 60-residue flexible linker. The two domains are structurally homologous, comprising a helical turn followed by two helices connected by an 11-12-residue loop. This motif is shared by subdomains of T4 endonuclease VII and transcription factor rho, despite negligible (< or =15%) sequence identity. NMR chemical shift mapping demonstrated that the LEM-domain binds BAF (barrier-to-autointegration factor), whereas LAP2-N binds DNA. Both binding surfaces comprise helix 1, the N-terminus of helix 2 and the inter-helical loop. Binding selectivity is determined by the nature of the surface residues in these binding sites, which are predominantly positively charged for LAP2-N and hydrophobic for the LEM-domain. Thus, LEM and LEM-like motifs form a common structure that evolution has customized for binding to BAF or DNA.

PubMed: 11500367
DOI: 10.1093/emboj/20.16.4399

Experimental method

SOLUTION NMR