ATLAS Run 2 searches for electroweak production of supersymmetric particles interpreted within the pMSSM

A summary of the constraints from searches performed by the ATLAS collaboration for the electroweak production of charginos and neutralinos is presented. Results from eight separate ATLAS searches are considered, each using 140 fb−1 of proton-proton data at a centre-of-mass energy of √ = 13 TeV collected at the Large Hadron Collider during its second data-taking run. The results are interpreted in the context of the 19-parameter phenomenological minimal supersymmetric standard model, where R-parity conservation is assumed and the lightest supersymmetric particle is assumed to be the lightest neutralino. Constraints from previous electroweak, flavour and dark matter related measurements are also considered. The results are presented in terms of constraints on supersymmetric particle masses and are compared with limits from simplified models. Also shown is the impact of ATLAS searches on parameters such as the dark matter relic density and the spin-dependent and spin-independent scattering cross-sections targeted by direct dark matter detection experiments. The Higgs boson and Z boson ‘funnel regions’, where a low-mass neutralino would not oversaturate the dark matter relic abundance, are almost completely excluded by the considered constraints. Example spectra for non-excluded supersymmetric models with light charginos and neutralinos are also presented

Structural analysis of regions predicted as unfolded at the nuclear envelope : example of emerin and lamin A.

Les lamines sont le principal composant du nucléosquelette. Elles sont principalement localisées à l’enveloppe nucléaire, où elles interagissent avec la membrane nucléaire interne, les protéines associées à la chromatine ainsi qu’avec des modulateurs de la signalisation cellulaire. Le gène LMNA code pour la prélamine A et la lamine C. La région C-terminale de la prélamine A est prédite pour être désordonnée et est la cible de plusieurs événements de maturation. En effet, la protéine est farnésylée, coupée, carboxyméthylée, puis coupée à nouveau ; perdant finalement son groupement farnésyl. Un mutant de cette protéine, dont 50 acides aminés sont manquants, est responsable du syndrome d’Huchtinson-Gilford, appelé progéria (Eriksson et al., 2003). Chez ce mutant, appelé progérine, le site de coupure finale est absent et la protéine reste constitutivement farnésylée. La lamine A est connue pour interagir avec la protéine de la membrane nucléaire interne, l’émerine. L’absence d’émerine est responsable de la dystrophie musculaire d’Emery Dreifuss. L’émerine contient un LEM, suivi d’une région prédite comme désordonnée, essentielle pour l’auto-assemblage de l’émerine (Berk et al., 2014). L’oligomérisation de l’émerine régule ses interactions avec plusieurs partenaires à la membrane nucléaire interne et à la chromatine. Nous avions auparavant démontré que la région nucléoplasmique de l’émerine peut s’auto-associer pour former des filaments in vitro (Herrada et al., 2015) et nous avons récemment révélé que ces filaments sont capables d’interagir directement avec la queue de la lamine A (Samson et al., 2018). Ici, je me suis intéressé à l’analyse structurale des régions prédites comme désordonnées chez (1) l’émerine (2) la prélamine A. Dans le cas de l’émerine, j’ai analysé la conformation de la région nucléoplasmique d’émerine avant et après auto-assemblage, en travaillant avec l’émerine sauvage et plusieurs mutants entraînant des myopathies. J’ai montré que deux fragments de l’émerine 1-187 et 67-221 peuvent polymériser, tandis que leur région commune 67-187, reste toujours monomérique dans nos conditions (Samson et al., 2018). Nous avons aussi montré que le domaine LEM est au moins partiellement déplié au cours de l’assemblage de la région 1-187. J’ai également attribué les signaux RMN de la région désordonnée 67-170, dans le but d’étudier par la suite l’impact des phosphorylations de cette région sur la structure de l’émerine et sur ses propriétés d’auto-assemblage (Samson et al., 2016). Dans le cas de la lamine A, j’ai étudié la région C-terminale de la prélamine A, prédite comme dépliée et qui est le siège de nombreuses modifications post-traductionnelles. J’ai attribué les signaux RMN du peptide prélamine A ainsi que de son mutant progérine (Celli et al., 2018). J’ai montré que ces deux peptides sont en effet déplés et possèdent une hélice transitoire très conservée. Je propose cette hélice comme site de liaison pour un partenaire encore non identifié. J’ai également démontré que le peptide prélamine A possède une tendance à s’auto-assembler. Cependant, la prélamine A et le peptide progérine sauvages et farnésylés, n’interagissent pas avec le domaine IgFold de la lamine A ni avec BAF, deux domaines associés avec la progéria. J’ai étudié par la suite les interactions de ces peptides avec deux autres partenaires associés à la progéria : la protéine de la membrane nucléaire interne SUN1 et la protéine associée à la chromatine RBBP4. SUN1 est également intrinsèquement désordonnée et très peu soluble dans nos conditions. Les résultats montrent que le peptide prélamine A ne lie pas RBBP4 mais pourrait avoir besoin de la partie C-terminale qui la précède. Cependant, RBBP4 lie directement le partenaire de la lamine BAF. Sur les bases de ces résultats, je propose une série d’expériences pour identifier les détails moléculaires des interactions entre la queue C-terminale de la lamine A, BAF et RBBP4.Lamins are the main components of the nucleoskeleton. They are primarily located at the nuclear envelope, where they interact with inner nuclear membrane proteins, chromatin-associated proteins and cell signaling modulators. The LMNA gene codes for prelamin A and lamin C. The C-terminal region of prelamin A is predicted to be unfolded and is the target of several maturation events. Indeed, the protein is farnesylated, cleaved, carboxymethylated and cleaved again; losing eventually its farnesyl group. A mutant of this protein, lacking 50 amino acids, is responsible for the Hutchinson-Gilford Progeria Syndrome (Eriksson et al., Nature 2003). In this mutant, called progerin, the final cleavage site is absent and the protein stays constitutively farnesylated. Lamin A is reported to interact with the inner nuclear membrane protein emerin. Lack of emerin is responsible for Emery Dreifuss Muscular Dystrophy. Emerin contains a folded LEM domain, followed by a region that is predicted to be disordered and is essential for emerin self-assembly (Berk et al., 2014). Emerin oligomerization regulates its interaction with several partners at the inner nuclear membrane and at the chromatin. We previously showed that the nucleoplasmic region of emerin can self-assemble to form curvilinear filaments in vitro (Herrada et al., 2015) and we recently revealed that these filaments are able to directly bind to the lamin A tail (Samson et al., 2018).Here I focused on the structural analysis of regions that are predicted to be unfolded in (1) emerin, (2) prelamin A. In the case of emerin, I analysed the conformation of the nucleoplasmic region of emerin before and after self-assembly, working on wild-type emerin as well as several mutants causing myopathies. I showed that the two fragments of emerin 1-187 and 67-221 were able to self-assemble, whereas their common region, 67-187, is always a monomer in our conditions (Samson et al., 2018). I also revealed that the LEM domain is at least partially unfolded during self-assembly of region 1-187, as a mutant with a destabilized LEM domain self-assembles faster and a mutant with a LEM domain locked in its folded conformation cannot self-assemble (Samson et al., 2017). I also assigned all the NMR signals of the unfolded region 67-170, in order to further study by NMR the impact of phosphorylation of this region on emerin structure and self-assembly properties (Samson et al., 2016). In the case of lamin A, I studied the C-terminal region of prelamin A that is predicted as unfolded and is heavily post-translationally modified. I assigned the NMR signals of this prelamin A peptide as well as its mutant peptide corresponding to the progerin sequence (Celli et al., 2018). I showed that both peptides are indeed unstructured and exhibit a partially populated helix that has a highly conserved sequence. I propose that this helix is a binding site for a yet unidentified partner. I also revealed that the prelamin A peptide has a tendency to self-assemble. However, the monomeric prelamin A and progerin peptides, wild-type as well as farnesylated, do not interact with the immunoglobulin-like domain of lamin A/C and with BAF, two domains associated with progeria. Then, I investigated the interactions mediated by these peptides and two other important partners associated to progeria: the inner nuclear membrane SUN1 and the chromatin-associated protein RBBP4. However, SUN1 is also intrinsically disordered and poorly soluble in our conditions. First results showed that the prelamin peptide does not bind to RBBP4 but might need the remaining part of the lamin A tail for this interaction. However, RBBP4 directly binds to the lamin partner BAF. Based on my results, I propose a set of experiments to identify the molecular details of the interactions between the lamin A tail, BAF and RBBP4

Analyse structurale des régions prédites comme dépliées de l’enveloppe nucléaire : exemple de l’émerine et de la lamine A.

Lamins are the main components of the nucleoskeleton. They are primarily located at the nuclear envelope, where they interact with inner nuclear membrane proteins, chromatin-associated proteins and cell signaling modulators. The LMNA gene codes for prelamin A and lamin C. The C-terminal region of prelamin A is predicted to be unfolded and is the target of several maturation events. Indeed, the protein is farnesylated, cleaved, carboxymethylated and cleaved again; losing eventually its farnesyl group. A mutant of this protein, lacking 50 amino acids, is responsible for the Hutchinson-Gilford Progeria Syndrome (Eriksson et al., Nature 2003). In this mutant, called progerin, the final cleavage site is absent and the protein stays constitutively farnesylated. Lamin A is reported to interact with the inner nuclear membrane protein emerin. Lack of emerin is responsible for Emery Dreifuss Muscular Dystrophy. Emerin contains a folded LEM domain, followed by a region that is predicted to be disordered and is essential for emerin self-assembly (Berk et al., 2014). Emerin oligomerization regulates its interaction with several partners at the inner nuclear membrane and at the chromatin. We previously showed that the nucleoplasmic region of emerin can self-assemble to form curvilinear filaments in vitro (Herrada et al., 2015) and we recently revealed that these filaments are able to directly bind to the lamin A tail (Samson et al., 2018).Here I focused on the structural analysis of regions that are predicted to be unfolded in (1) emerin, (2) prelamin A. In the case of emerin, I analysed the conformation of the nucleoplasmic region of emerin before and after self-assembly, working on wild-type emerin as well as several mutants causing myopathies. I showed that the two fragments of emerin 1-187 and 67-221 were able to self-assemble, whereas their common region, 67-187, is always a monomer in our conditions (Samson et al., 2018). I also revealed that the LEM domain is at least partially unfolded during self-assembly of region 1-187, as a mutant with a destabilized LEM domain self-assembles faster and a mutant with a LEM domain locked in its folded conformation cannot self-assemble (Samson et al., 2017). I also assigned all the NMR signals of the unfolded region 67-170, in order to further study by NMR the impact of phosphorylation of this region on emerin structure and self-assembly properties (Samson et al., 2016). In the case of lamin A, I studied the C-terminal region of prelamin A that is predicted as unfolded and is heavily post-translationally modified. I assigned the NMR signals of this prelamin A peptide as well as its mutant peptide corresponding to the progerin sequence (Celli et al., 2018). I showed that both peptides are indeed unstructured and exhibit a partially populated helix that has a highly conserved sequence. I propose that this helix is a binding site for a yet unidentified partner. I also revealed that the prelamin A peptide has a tendency to self-assemble. However, the monomeric prelamin A and progerin peptides, wild-type as well as farnesylated, do not interact with the immunoglobulin-like domain of lamin A/C and with BAF, two domains associated with progeria. Then, I investigated the interactions mediated by these peptides and two other important partners associated to progeria: the inner nuclear membrane SUN1 and the chromatin-associated protein RBBP4. However, SUN1 is also intrinsically disordered and poorly soluble in our conditions. First results showed that the prelamin peptide does not bind to RBBP4 but might need the remaining part of the lamin A tail for this interaction. However, RBBP4 directly binds to the lamin partner BAF. Based on my results, I propose a set of experiments to identify the molecular details of the interactions between the lamin A tail, BAF and RBBP4.Les lamines sont le principal composant du nucléosquelette. Elles sont principalement localisées à l’enveloppe nucléaire, où elles interagissent avec la membrane nucléaire interne, les protéines associées à la chromatine ainsi qu’avec des modulateurs de la signalisation cellulaire. Le gène LMNA code pour la prélamine A et la lamine C. La région C-terminale de la prélamine A est prédite pour être désordonnée et est la cible de plusieurs événements de maturation. En effet, la protéine est farnésylée, coupée, carboxyméthylée, puis coupée à nouveau ; perdant finalement son groupement farnésyl. Un mutant de cette protéine, dont 50 acides aminés sont manquants, est responsable du syndrome d’Huchtinson-Gilford, appelé progéria (Eriksson et al., 2003). Chez ce mutant, appelé progérine, le site de coupure finale est absent et la protéine reste constitutivement farnésylée. La lamine A est connue pour interagir avec la protéine de la membrane nucléaire interne, l’émerine. L’absence d’émerine est responsable de la dystrophie musculaire d’Emery Dreifuss. L’émerine contient un LEM, suivi d’une région prédite comme désordonnée, essentielle pour l’auto-assemblage de l’émerine (Berk et al., 2014). L’oligomérisation de l’émerine régule ses interactions avec plusieurs partenaires à la membrane nucléaire interne et à la chromatine. Nous avions auparavant démontré que la région nucléoplasmique de l’émerine peut s’auto-associer pour former des filaments in vitro (Herrada et al., 2015) et nous avons récemment révélé que ces filaments sont capables d’interagir directement avec la queue de la lamine A (Samson et al., 2018). Ici, je me suis intéressé à l’analyse structurale des régions prédites comme désordonnées chez (1) l’émerine (2) la prélamine A. Dans le cas de l’émerine, j’ai analysé la conformation de la région nucléoplasmique d’émerine avant et après auto-assemblage, en travaillant avec l’émerine sauvage et plusieurs mutants entraînant des myopathies. J’ai montré que deux fragments de l’émerine 1-187 et 67-221 peuvent polymériser, tandis que leur région commune 67-187, reste toujours monomérique dans nos conditions (Samson et al., 2018). Nous avons aussi montré que le domaine LEM est au moins partiellement déplié au cours de l’assemblage de la région 1-187. J’ai également attribué les signaux RMN de la région désordonnée 67-170, dans le but d’étudier par la suite l’impact des phosphorylations de cette région sur la structure de l’émerine et sur ses propriétés d’auto-assemblage (Samson et al., 2016). Dans le cas de la lamine A, j’ai étudié la région C-terminale de la prélamine A, prédite comme dépliée et qui est le siège de nombreuses modifications post-traductionnelles. J’ai attribué les signaux RMN du peptide prélamine A ainsi que de son mutant progérine (Celli et al., 2018). J’ai montré que ces deux peptides sont en effet déplés et possèdent une hélice transitoire très conservée. Je propose cette hélice comme site de liaison pour un partenaire encore non identifié. J’ai également démontré que le peptide prélamine A possède une tendance à s’auto-assembler. Cependant, la prélamine A et le peptide progérine sauvages et farnésylés, n’interagissent pas avec le domaine IgFold de la lamine A ni avec BAF, deux domaines associés avec la progéria. J’ai étudié par la suite les interactions de ces peptides avec deux autres partenaires associés à la progéria : la protéine de la membrane nucléaire interne SUN1 et la protéine associée à la chromatine RBBP4. SUN1 est également intrinsèquement désordonnée et très peu soluble dans nos conditions. Les résultats montrent que le peptide prélamine A ne lie pas RBBP4 mais pourrait avoir besoin de la partie C-terminale qui la précède. Cependant, RBBP4 lie directement le partenaire de la lamine BAF. Sur les bases de ces résultats, je propose une série d’expériences pour identifier les détails moléculaires des interactions entre la queue C-terminale de la lamine A, BAF et RBBP4

1H, 13C and 15N backbone resonance assignment of the intrinsically disordered region of the nuclear envelope protein emerin.

International audienceHuman emerin is an inner nuclear membrane protein involved in the response of the nucleus to mechanical stress. It contributes to the physical connection between the cytoskeleton and the nucleoskeleton. It is also involved in chromatin organization. Its N-terminal region is nucleoplasmic and comprises a globular LEM domain from residue 1 to residue 43. The three-dimensional structure of this LEM domain in complex with the chromatin BAF protein was solved from NMR data. Apart from the LEM domain, the nucleoplasmic region of emerin, from residue 44 to residue 221, is predicted to be intrinsically disordered. Mutations in this region impair binding to several emerin partners as lamin A, actin or HDAC3. However the molecular details of these recognition defects are unknown. Here we report (1)H, (15)N, (13)CO, (13)Cα and (13)Cβ NMR chemical shift assignments of the emerin fragment from residue 67 to residue 170, which is sufficient for nuclear localization and involved in lamin A binding. Chemical shift analysis confirms that this fragment is intrinsically disordered in 0 and 8 M urea

H-1, C-13 and N-15 backbone resonance assignment of the lamin C-terminal region specific to prelamin A

International audienceLamins are the main components of the nucleoskeleton. They form a protein meshwork that underlies the inner nuclear membrane. Mutations in the LMNA gene coding for A-type lamins (lamins A and C) cause a large panel of human diseases, referred to as laminopathies. These diseases include muscular dystrophies, lipodystrophies and premature aging diseases. Lamin A exhibits a C-terminal region that is different from lamin C and is post-translationally modified. It is produced as prelamin A and it is then farnesylated, cleaved, carboxymethylated and cleaved again in order to become mature lamin A. In patients with the severe Hutchinson-Gilford progeria syndrome, a specific single point mutation in LMNA leads to an aberrant splicing of the LMNA gene preventing the post-translational processing of prelamin A. This leads to the accumulation of a permanently farnesylated lamin A mutant lacking 50 amino acids named progerin. We here report the NMR H-1, N-15, (CO)-C-13, C-13 and C-13 chemical shift assignment of the C-terminal region that is specific to prelamin A, from amino acid 567 to amino acid 664. We also report the NMR H-1, N-15, (CO)-C-13, C-13 and C-13 chemical shift assignment of the C-terminal region of the progerin variant, from amino acid 567 to amino acid 614. Analysis of these chemical shift data confirms that both prelamin A and progerin C-terminal domains are largely disordered and identifies a common partially populated -helix from amino acid 576 to amino acid 585. This helix is well conserved from fishes to mammals

Structural analysis of the ternary complex between lamin A/C, BAF and emerin identifies an interface disrupted in autosomal recessive progeroid diseases

International audienceLamins are the main components of the nucleoskeleton. Whereas their 3D organization was recently described using cryoelectron tomography, no structural data highlights how they interact with their partners at the interface between the inner nuclear envelope and chromatin. A large number of mutations causing rare genetic disorders called laminopathies were identified in the C-terminal globular Igfold domain of lamins A and C. We here present a first structural description of the interaction between the lamin A/C immunoglobulin-like domain and emerin, a nuclear envelope protein. We reveal that this lamin A/C domain both directly binds self-assembled emerin and interacts with monomeric emerin LEM domain through the dimeric chromatin-associated Barrier-to-Autointegration Factor (BAF) protein. Mutations causing autosomal recessive progeroid syndromes specifically impair proper binding of lamin A/C domain to BAF, thus destabilizing the link between lamin A/C and BAF in cells. Recent data revealed that, during nuclear assembly, BAF's ability to bridge distant DNA sites is essential for guiding membranes to form a single nucleus around the mitotic chromosome ensemble. Our results suggest that BAF interaction with lamin A/C also plays an essential role, and that mutations associated with progeroid syndromes leads to a dysregulation of BAF-mediated chromatin organization and gene expression

18F-NaF PET/CT: EANM procedure guidelines for bone imaging

The aim of this guideline is to provide minimum standards for the performance and interpretation of (18)F-NaF PET/CT scans. Standard acquisition and interpretation of nuclear imaging modalities will help to provide consistent data acquisition and numeric values between different platforms and institutes and to promote the use of PET/CT modality as an established diagnostic modality in routine clinical practice. This will also improve the value of scientific work and its contribution to evidence-based medicine

Emerin self‐assembly mechanism: role of the LEM domain

International audienceAt the nuclear envelope, the inner nuclear membrane protein emerin contributes to the interface between the nucleoskeleton and the chromatin. Emerin is an essential actor of the nuclear response to a mechanical signal. Genetic defects in emerin cause Emery-Dreifuss muscular dystrophy. It was proposed that emerin oligomerization regulates nucleoskeleton binding , and impaired oligomerization contributes to the loss of function of emerin disease-causing mutants. We here report the first structural characterization of emerin oligomers. We identified an N-terminal emerin region from amino acid 1 to amino acid 132 that is necessary and sufficient for formation of long curvilinear filaments. In emerin monomer, this region contains a globular LEM domain and a fragment that is intrinsically disordered. Solid-state nuclear magnetic resonance analysis identifies the LEM b-fragment as part of the oligomeric structural core. However, the LEM domain alone does not self-assemble into filaments. Additional residues forming a b-structure are observed within the filaments that could correspond to the unstructured region in emerin monomer. We show that the delK37 mutation causing muscular dystrophy triggers LEM domain unfolding and increases emerin self-assembly rate. Similarly, inserting a disulfide bridge that stabilizes the LEM folded state impairs emerin N-terminal region self-assembly, whereas reducing this disulfide bridge triggers self-assembly. We conclude that the LEM domain, responsible for binding to the chromatin protein BAF, undergoes a conformational change during self-assembly of emerin N-terminal region. The consequences of these structural rearrangement and self-assembly events on emerin binding properties are discussed. Abbreviations BAF, barrier-to-autointegration factor; DTT, dithiothreitol; EDMD, Emery-Dreifuss muscular dystrophy; LEM, Lap2-emerin-Man1; LINC, linker of nucleoskeleton and cytoskeleton; NMR, nuclear magnetic resonance; SDS/PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; ThT, thioflavin T

Emerin self‐assembly mechanism: role of the LEM domain

International audienceAt the nuclear envelope, the inner nuclear membrane protein emerin contributes to the interface between the nucleoskeleton and the chromatin. Emerin is an essential actor of the nuclear response to a mechanical signal. Genetic defects in emerin cause Emery-Dreifuss muscular dystrophy. It was proposed that emerin oligomerization regulates nucleoskeleton binding , and impaired oligomerization contributes to the loss of function of emerin disease-causing mutants. We here report the first structural characterization of emerin oligomers. We identified an N-terminal emerin region from amino acid 1 to amino acid 132 that is necessary and sufficient for formation of long curvilinear filaments. In emerin monomer, this region contains a globular LEM domain and a fragment that is intrinsically disordered. Solid-state nuclear magnetic resonance analysis identifies the LEM b-fragment as part of the oligomeric structural core. However, the LEM domain alone does not self-assemble into filaments. Additional residues forming a b-structure are observed within the filaments that could correspond to the unstructured region in emerin monomer. We show that the delK37 mutation causing muscular dystrophy triggers LEM domain unfolding and increases emerin self-assembly rate. Similarly, inserting a disulfide bridge that stabilizes the LEM folded state impairs emerin N-terminal region self-assembly, whereas reducing this disulfide bridge triggers self-assembly. We conclude that the LEM domain, responsible for binding to the chromatin protein BAF, undergoes a conformational change during self-assembly of emerin N-terminal region. The consequences of these structural rearrangement and self-assembly events on emerin binding properties are discussed. Abbreviations BAF, barrier-to-autointegration factor; DTT, dithiothreitol; EDMD, Emery-Dreifuss muscular dystrophy; LEM, Lap2-emerin-Man1; LINC, linker of nucleoskeleton and cytoskeleton; NMR, nuclear magnetic resonance; SDS/PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; ThT, thioflavin T

Emerin self‐assembly mechanism: role of the LEM domain

International audienceAt the nuclear envelope, the inner nuclear membrane protein emerin contributes to the interface between the nucleoskeleton and the chromatin. Emerin is an essential actor of the nuclear response to a mechanical signal. Genetic defects in emerin cause Emery-Dreifuss muscular dystrophy. It was proposed that emerin oligomerization regulates nucleoskeleton binding , and impaired oligomerization contributes to the loss of function of emerin disease-causing mutants. We here report the first structural characterization of emerin oligomers. We identified an N-terminal emerin region from amino acid 1 to amino acid 132 that is necessary and sufficient for formation of long curvilinear filaments. In emerin monomer, this region contains a globular LEM domain and a fragment that is intrinsically disordered. Solid-state nuclear magnetic resonance analysis identifies the LEM b-fragment as part of the oligomeric structural core. However, the LEM domain alone does not self-assemble into filaments. Additional residues forming a b-structure are observed within the filaments that could correspond to the unstructured region in emerin monomer. We show that the delK37 mutation causing muscular dystrophy triggers LEM domain unfolding and increases emerin self-assembly rate. Similarly, inserting a disulfide bridge that stabilizes the LEM folded state impairs emerin N-terminal region self-assembly, whereas reducing this disulfide bridge triggers self-assembly. We conclude that the LEM domain, responsible for binding to the chromatin protein BAF, undergoes a conformational change during self-assembly of emerin N-terminal region. The consequences of these structural rearrangement and self-assembly events on emerin binding properties are discussed. Abbreviations BAF, barrier-to-autointegration factor; DTT, dithiothreitol; EDMD, Emery-Dreifuss muscular dystrophy; LEM, Lap2-emerin-Man1; LINC, linker of nucleoskeleton and cytoskeleton; NMR, nuclear magnetic resonance; SDS/PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; ThT, thioflavin T