2odc
LEM-domain of the nuclear envelope protein emerin
Structural highlights
DiseaseEMD_HUMAN Defects in EMD are the cause of Emery-Dreifuss muscular dystrophy type 1 (EDMD1) [MIM:310300. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.[1] [2] [3] [4] FunctionEMD_HUMAN Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. Required for proper localization of non-farnesylated prelamin-A/C.[5] [6] [7] [8] [9] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe barrier-to-autointegration factor BAF binds to the LEM domain (Em(LEM)) of the nuclear envelope protein emerin and plays an essential role in the nuclear architecture of metazoan cells. In addition, the BAF(2) dimer bridges and compacts double-stranded DNA nonspecifically via two symmetry-related DNA binding sites. In this article we present biophysical and structural studies on a complex of BAF(2) and Em(LEM). Light scattering, analytical ultracentrifugation, and NMR indicate a stoichiometry of one molecule of Em(LEM) bound per BAF(2) dimer. The equilibrium dissociation constant (K(d)) for the interaction of the BAF(2) dimer and Em(LEM), determined by isothermal titration calorimetry, is 0.59 +/- 0.03 microm. Z-exchange spectroscopy between corresponding cross-peaks of the magnetically non-equivalent subunits of the BAF(2) dimer in the complex yields a dissociation rate constant of 78 +/- 2s(-1). The solution NMR structure of the BAF(2)-Em(LEM) complex reveals that the LEM and DNA binding sites on BAF(2) are non-overlapping and that both subunits of the BAF(2) dimer contribute approximately equally to the Em(LEM) binding site. The relevance of the implications of the structural and biophysical data on the complex in the context of the interaction between the BAF(2) dimer and Em(LEM) at the nuclear envelope is discussed. Solution NMR structure of the barrier-to-autointegration factor-Emerin complex.,Cai M, Huang Y, Suh JY, Louis JM, Ghirlando R, Craigie R, Clore GM J Biol Chem. 2007 May 11;282(19):14525-35. Epub 2007 Mar 13. PMID:17355960[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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