title: The molecular basis of emerin-emerin and emerin-BAF interactions.
abstract: Emerin is a conserved membrane component of nuclear lamina structure. Here, we report an advance in understanding the molecular basis of emerin function: intermolecular emerin-emerin association. There were two modes: one mediated by association of residues 170-220 in one emerin molecule to residues 170-220 in another, and the second involving residues 170-220 and 1-132. Deletion analysis showed residues 187-220 contain a positive element essential for intermolecular association in cells. By contrast, deletion of residues 168-186 inactivated a proposed negative element, required to limit or control association. Association of GFP-emerin with nuclear BAF in cells required the LEM domain (residues 1-47) and the positive element. Emerin peptide arrays revealed direct binding of residues 170-220 to residues 206-225 (the proposed positive element), residues 147-174 (particularly P(153)MYGRDSAYQSITHYRP(169)) and the LEM domain. Emerin residues 1-132 and 159-220 were each sufficient to bind lamin A or B1 tails in vitro, identifying two independent regions of molecular contact with lamins. These results, and predicted emerin intrinsic disorder, support the hypothesis that there are multiple 'backbone' and LEM-domain configurations in a proposed intermolecular emerin network at the nuclear envelope.
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 USA.
authors: Jason M
authors: JM
authors: Berk
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 USA.
authors: Dan N
authors: DN
authors: Simon
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 USA.
authors: Clifton R
authors: CR
authors: Jenkins-Houk
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 USA.
authors: Jason W
authors: JW
authors: Westerbeck
authors: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors: Line M
authors: LM
authors: Grønning-Wang
authors: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0450 Oslo, Norway.
authors: Cathrine R
authors: CR
authors: Carlson
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 USA klwilson@jhmi.edu.
authors: Katherine L
authors: KL
authors: Wilson
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D034881:Nuclear Lamina / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin
keywords: Barrier to autointegration factor; Emerin; Emery-Dreifuss muscular dystrophy; LEM domain; Lamin; Nestor-Guillermo progeria; Nuclear envelope; Nuclear lamina; Nucleoskeleton