Skeletal Muscle Dystrophy mutant of lamin A alters the structure and dynamics of the Ig fold domain

Scientific Reports
Subarna DuttaKaushik Sengupta

Abstract

Mutations in the different domains of A-type lamin proteins cause a diverse plethora of diseases collectively termed as laminopathies which can affect multiple organs. Ig fold is one such domain of lamin A which is implicated in numerous nuclear interactions wherein the mutations lead to different laminopathies. W514R is one such mutation in the Ig fold which leads to severe phenotypes in Skeletal Muscle Dystrophy (SMD) which is a class of laminopathies. In this report, we elucidated gross alterations in structure and dynamics at the level of individual amino acids. These studies indicate altered conformational features of residues in the close vicinity of W514. Imaging of mammalian cells transfected with the mutant have shown distinct perturbation of the nuclear meshwork with concomitant alteration in nuclear interactions as a result of increased oligomerization of Ig W514R. Hence, this novel approach of amalgamating theoretical and experimental procedures to predict the severity of a mutant in the context of laminopathies could be extended for numerous lamin A mutants.

References

Jan 1, 1988·Annual Review of Immunology·A F Williams, A N Barclay
Nov 1, 1993·Journal of Biomolecular NMR·A C Wang, A Bax
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Apr 19, 1996·The Journal of Biological Chemistry·B M MachielsJ L Broers
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Dec 22, 1999·Journal of Molecular Biology·D SeptJ A McCammon
Apr 8, 2000·Current Opinion in Structural Biology·H J Berendsen, S Hayward
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Mar 20, 2002·The Journal of Biological Chemistry·Sirano Dhe-PaganonSteven E Shoelson
May 23, 2002·Journal of Biomolecular NMR·Isabelle KrimmSophie Zinn-Justin
May 13, 2003·The Journal of Biological Chemistry·Primoz PristovsekFrank Bernhard
Jun 24, 2004·Journal of Biomolecular NMR·Andreas MuranyiA Kristina Downing
Jul 21, 2004·Journal of Computational Chemistry·Chris OostenbrinkWilfred F van Gunsteren
Sep 24, 2005·Stem Cells·Dan ConstantinescuAntonei B Csoka
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Jul 11, 2006·The Journal of Biological Chemistry·Jan LammerdingRichard T Lee
Aug 11, 2006·Journal of Cell Science·Antonio E Rusiñol, Michael S Sinensky
Sep 26, 2006·Biophysical Journal·A C RowatJ H Ipsen
Nov 23, 2006·Journal of Biomechanics·Ashkan Vaziri, Mohammad R Kaazempur Mofrad
Apr 25, 2007·Experimental Cell Research·Eric C Schirmer, Roland Foisner
Jun 6, 2007·Nature Reviews. Genetics·Asifa Akhtar, Susan M Gasser
Mar 15, 2008·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Agnieszka Madej-PilarczykIrena Hausmanowa-Petrusewicz
Apr 23, 2008·The Journal of Cell Biology·Dale K ShumakerRobert D Goldman
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Howard J WormanYuexia Wang
May 11, 2010·Cold Spring Harbor Perspectives in Biology·Katherine L Wilson, Roland Foisner
Feb 4, 2011·Molecular Biology of the Cell·Yvonne C LussiBirthe Fahrenkrog
Mar 24, 2011·Future Medicinal Chemistry·Predrag Kukić, Jens Erik Nielsen
Jun 4, 2011·Journal of Structural Biology·Zhao QinMarkus J Buehler
Oct 11, 2011·Nucleus·Teiba Al-HaboubiBirthe Fahrenkrog
Dec 1, 2011·Nucleus·Shao H YangStephen G Young
Jan 18, 2013·Nucleus·Melanie A Eckersley-MaslinDavid L Spector
Mar 19, 2013·Cell·Katherine H Schreiber, Brian K Kennedy
May 25, 2013·Biochemistry·Pritha BhattacharjeeKaushik Sengupta
Jan 1, 2014·Seminars in Cell & Developmental Biology·Kevin GessonRoland Foisner

❮ Previous
Next ❯

Citations

May 28, 2020·Cells·Francesca DonnalojaManuela Teresa Raimondi
Dec 8, 2020·Emerging Topics in Life Sciences·Chandrayee MukherjeeKaushik Sengupta
Nov 16, 2020·Current Opinion in Cell Biology·Sherif A EldiranyChristopher G Bunick

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
X-Ray
fluorescence spectroscopy
Fluorescence
light scattering
differential scanning calorimetry
PCR
size exclusion chromatography
PCA
transfection

Software Mentioned

r2r1
GROMOS96
Sparky
NIS Elements
pymol
pdbinertia
tm
VMD
GROMACS
APBS

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.