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Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM‐domain structures: one binds BAF and the other binds DNA
Author(s) -
Cai Mengli,
Huang Ying,
Ghirlando Rodolfo,
Wilson Katherine L.,
Craigie Robert,
Clore G.Marius
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.16.4399
Subject(s) - biology , dna , envelope (radar) , constant (computer programming) , domain (mathematical analysis) , biophysics , dna binding protein , nuclear protein , protein structure , microbiology and biotechnology , genetics , biochemistry , gene , transcription factor , computer science , telecommunications , mathematical analysis , radar , mathematics , programming language
The nuclear envelope proteins L AP2, e merin and M AN1 share a conserved ∼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 ∼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 (≤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.