6RPR

LEM domain of Emerin mutant T43I in complex with BAF dimer and the Igfold of the lamin A/C

6RPR の概要

• エントリーDOI: 10.2210/pdb6rpr/pdb
• 分子名称: Prelamin-A/C, barrier to autointegration factor (BAF), LEM domain of emerin mutant T43I, ... (5 entities in total)
• 機能のキーワード: nuclear membrane protein, dna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 37782.51

構造登録者

Essawy, N.,Samson, C. (登録日: 2019-05-14, 公開日: 2020-03-04, 最終更新日: 2024-01-24)

主引用文献

Essawy, N.,Samson, C.,Petitalot, A.,Moog, S.,Bigot, A.,Herrada, I.,Marcelot, A.,Arteni, A.A.,Coirault, C.,Zinn-Justin, S.
An Emerin LEM-Domain Mutation Impairs Cell Response to Mechanical Stress.
Cells, 8:-, 2019

PubMed Abstract: Emerin is a nuclear envelope protein that contributes to genome organization and cell mechanics. Through its N-terminal LAP2-emerin-MAN1 (LEM)-domain, emerin interacts with the DNA-binding protein barrier-to-autointegration (BAF). Emerin also binds to members of the linker of the nucleoskeleton and cytoskeleton (LINC) complex. Mutations in the gene encoding emerin are responsible for the majority of cases of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD). Most of these mutations lead to an absence of emerin. A few missense and short deletion mutations in the disordered region of emerin are also associated with X-EDMD. More recently, missense and short deletion mutations P22L, ∆K37 and T43I were discovered in emerin LEM-domain, associated with isolated atrial cardiac defects (ACD). Here we reveal which defects, at both the molecular and cellular levels, are elicited by these LEM-domain mutations. Whereas K37 mutation impaired the correct folding of the LEM-domain, P22L and T43I had no impact on the 3D structure of emerin. Surprisingly, all three mutants bound to BAF, albeit with a weaker affinity in the case of K37. In human myofibroblasts derived from a patient's fibroblasts, emerin ∆K37 was correctly localized at the inner nuclear membrane, but was present at a significantly lower level, indicating that this mutant is abnormally degraded. Moreover, SUN2 was reduced, and these cells were defective in producing actin stress fibers when grown on a stiff substrate and after cyclic stretches. Altogether, our data suggest that the main effect of mutation K37 is to perturb emerin function within the LINC complex in response to mechanical stress.

PubMed: 31185657
DOI: 10.3390/cells8060570

実験手法

X-RAY DIFFRACTION (2.26 Å)