File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1016/j.bbrc.2019.02.138
- Scopus: eid_2-s2.0-85063608253
- PMID: 30853177
- WOS: WOS:000465063700004
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Structural instability of lamin A tail domain modulates its assembly and higher order function in Emery–Dreifuss muscular dystrophy
Title | Structural instability of lamin A tail domain modulates its assembly and higher order function in Emery–Dreifuss muscular dystrophy |
---|---|
Authors | |
Keywords | Ig-domain Lamin A Laminopathy Thermal stability |
Issue Date | 2019 |
Publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description |
Citation | Biochemical and Biophysical Research Communications, 2019, v. 512 n. 1, p. 22-28 How to Cite? |
Abstract | The C-terminal Ig-domain of lamin A plays critical roles in cell function via interaction with proteins, DNA, and chromatin. Mutations in this domain are known to cause various diseases including Emery–Dreifuss muscular dystrophy (EDMD) and familial partial lipodystrophy (FPLD). Here we examined the biophysical and biochemical properties of mutant Ig-domains identified in patients with EDMD and FPLD. EDMD-related mutant Ig-domain showed decreased stability to heat and denaturant. This result was also confirmed by experiments using full-length mutant lamin A, although the decrease in melting temperature was much less than that of the mutant Ig-domain alone. The unstable EDMD Ig-domain disrupted the proper assembly of lamin A, resulting in abnormal paracrystal formation and decreased viscosity. In contrast, FPLD-related mutant Ig-domains were thermally stable, although they lost DNA binding function. Alanine substitution experiments revealed a functional domain of DNA binding in the Ig-domain. Thus, the overall biophysical property of Ig-domains is closely associated with clinical phenotype. |
Persistent Identifier | http://hdl.handle.net/10722/276087 |
ISSN | 2023 Impact Factor: 2.5 2023 SCImago Journal Rankings: 0.770 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Mio, M | - |
dc.contributor.author | Sugiki, T | - |
dc.contributor.author | Matsuda, C | - |
dc.contributor.author | Mitsuhashi, H | - |
dc.contributor.author | Kojima, C | - |
dc.contributor.author | Chan, SY | - |
dc.contributor.author | Hayashi, YK | - |
dc.contributor.author | Mio, K | - |
dc.date.accessioned | 2019-09-10T02:55:41Z | - |
dc.date.available | 2019-09-10T02:55:41Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Biochemical and Biophysical Research Communications, 2019, v. 512 n. 1, p. 22-28 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | http://hdl.handle.net/10722/276087 | - |
dc.description.abstract | The C-terminal Ig-domain of lamin A plays critical roles in cell function via interaction with proteins, DNA, and chromatin. Mutations in this domain are known to cause various diseases including Emery–Dreifuss muscular dystrophy (EDMD) and familial partial lipodystrophy (FPLD). Here we examined the biophysical and biochemical properties of mutant Ig-domains identified in patients with EDMD and FPLD. EDMD-related mutant Ig-domain showed decreased stability to heat and denaturant. This result was also confirmed by experiments using full-length mutant lamin A, although the decrease in melting temperature was much less than that of the mutant Ig-domain alone. The unstable EDMD Ig-domain disrupted the proper assembly of lamin A, resulting in abnormal paracrystal formation and decreased viscosity. In contrast, FPLD-related mutant Ig-domains were thermally stable, although they lost DNA binding function. Alanine substitution experiments revealed a functional domain of DNA binding in the Ig-domain. Thus, the overall biophysical property of Ig-domains is closely associated with clinical phenotype. | - |
dc.language | eng | - |
dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description | - |
dc.relation.ispartof | Biochemical and Biophysical Research Communications | - |
dc.subject | Ig-domain | - |
dc.subject | Lamin A | - |
dc.subject | Laminopathy | - |
dc.subject | Thermal stability | - |
dc.title | Structural instability of lamin A tail domain modulates its assembly and higher order function in Emery–Dreifuss muscular dystrophy | - |
dc.type | Article | - |
dc.identifier.email | Chan, SY: sychan@hkucc.hku.hk | - |
dc.identifier.authority | Chan, SY=rp00356 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.bbrc.2019.02.138 | - |
dc.identifier.pmid | 30853177 | - |
dc.identifier.scopus | eid_2-s2.0-85063608253 | - |
dc.identifier.hkuros | 303048 | - |
dc.identifier.volume | 512 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 22 | - |
dc.identifier.epage | 28 | - |
dc.identifier.isi | WOS:000465063700004 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0006-291X | - |