TY - JOUR
T1 - Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF
AU - Lee, Kenneth K.
AU - Haraguchi, Tokuko
AU - Lee, Richard S.
AU - Koujin, Takako
AU - Hiraoka, Yasushi
AU - Wilson, Katherine L.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Loss of emerin, a lamin-binding nuclear membrane protein, causes Emery-Dreifuss muscular dystrophy. We analyzed 13 site-directed mutations, and four disease-causing mutations that do not disrupt emerin stability or localization. We show that emerin binds directly to barrier-to-autointegration factor (BAF), a DNA-bridging protein, and that this binding to BAF requires conserved residues in the LEM-motif of emerin. Emerin has two distinct functional domains: the LEM-domain at the N-terminus, which mediates binding to BAF, and a second functional domain in the central region, which mediates binding to lamin A. Disease mutation Δ95-99 mapped to the lamin-binding domain and disrupted lamin A binding in vitro. Two other disease-linked residues, Ser54 and Pro183, mapped outside the BAF and lamin-binding domains, suggesting that emerin may have additional functional domains relevant to disease. The disease-linked emerin proteins all remained active for binding to BAF, both in vitro and in vivo, suggesting that disease can result from the loss of specific molecular interactions between emerin and either lamin A or putative novel partner(s). The demonstration that emerin binds directly to BAF, coupled to similar results for LAP2, provides proof in principle that all LEM-domain nuclear proteins can interact with BAF, with interesting implications for chromatin attachment to the nuclear envelope.
AB - Loss of emerin, a lamin-binding nuclear membrane protein, causes Emery-Dreifuss muscular dystrophy. We analyzed 13 site-directed mutations, and four disease-causing mutations that do not disrupt emerin stability or localization. We show that emerin binds directly to barrier-to-autointegration factor (BAF), a DNA-bridging protein, and that this binding to BAF requires conserved residues in the LEM-motif of emerin. Emerin has two distinct functional domains: the LEM-domain at the N-terminus, which mediates binding to BAF, and a second functional domain in the central region, which mediates binding to lamin A. Disease mutation Δ95-99 mapped to the lamin-binding domain and disrupted lamin A binding in vitro. Two other disease-linked residues, Ser54 and Pro183, mapped outside the BAF and lamin-binding domains, suggesting that emerin may have additional functional domains relevant to disease. The disease-linked emerin proteins all remained active for binding to BAF, both in vitro and in vivo, suggesting that disease can result from the loss of specific molecular interactions between emerin and either lamin A or putative novel partner(s). The demonstration that emerin binds directly to BAF, coupled to similar results for LAP2, provides proof in principle that all LEM-domain nuclear proteins can interact with BAF, with interesting implications for chromatin attachment to the nuclear envelope.
KW - Barrier to autointegration factor
KW - Emery-Dreifuss muscular dystrophy
KW - LEM-domain
KW - Lamin A
KW - Lamin-associated polypeptide 2
KW - MAN1
KW - Nuclear envelope
KW - Nuclear lamina
UR - http://www.scopus.com/inward/record.url?scp=0035694820&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035694820&partnerID=8YFLogxK
M3 - Article
C2 - 11792821
AN - SCOPUS:0035694820
SN - 0021-9533
VL - 114
SP - 4567
EP - 4573
JO - Journal of cell science
JF - Journal of cell science
IS - 24
ER -