Direct binding of nuclear membrane protein MAN1 to emerin in vitro and two modes of binding to barrier-to-autointegration factor

Malini Mansharamani, Katherine L. Wilson

Research output: Contribution to journalArticle

Abstract

MAN1 is a vertebrate nuclear inner membrane protein that inhibits Smad signaling downstream of transforming growth factor β. MAN1 has an exposed LEM domain-containing N-terminal region ("MAN1-N"), two transmembrane domains, and an exposed C-terminal domain ("MAN1-C"). Many regions of human MAN1 are homologous to emerin, a LEM domain nuclear protein, loss of which causes Emery-Dreifuss muscular dystrophy (EDMD). To test the hypothesis that MAN1 function might overlap with emerin, we tested different polypeptide fragments of MAN1 for binding to selected partners of emerin. Our findings support this hypothesis. Blot overlay assays and co-immunoprecipitation studies showed that MAN1-C binds the transcription regulators GCL, Btf, and barrier-to-autointegration factor (BAF). BAF binding to this region, which has no LEM domain, was notable. Sequence alignments identified a potential BAF-binding motif, characterized by the conserved residues Ser-Arg-Val, in MAN1-C and two other BAF-binding proteins. The other region, MAN1-N, bound directly to BAF, lamin A, and lamin B1, supporting functional overlap with emerin. Unexpectedly, three independent assays showed that MAN1-N also bound directly to emerin. Proposed MAN1-emerin complexes are discussed in the context of EDMD disease mechanisms and potential in vivo functions.

Original languageEnglish (US)
Pages (from-to)13863-13870
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number14
DOIs
StatePublished - Apr 8 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Direct binding of nuclear membrane protein MAN1 to emerin in vitro and two modes of binding to barrier-to-autointegration factor'. Together they form a unique fingerprint.

  • Cite this