1gjj

From Proteopedia

N-TERMINAL CONSTANT REGION OF THE NUCLEAR ENVELOPE PROTEIN LAP2

Overview

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.

Disease

Known disease associated with this structure: Cardiomyopathy, dilated, 1T OMIM:[188380]

About this Structure

1GJJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA., Cai M, Huang Y, Ghirlando R, Wilson KL, Craigie R, Clore GM, EMBO J. 2001 Aug 15;20(16):4399-407. PMID:11500367

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