+データを開く
-基本情報
登録情報 | データベース: SASBDB / ID: SASDB83 |
---|---|
試料 | Human dystrophin central domain repeats 16 to 17
|
機能・相同性 | 機能・相同性情報 regulation of muscle system process / regulation of cellular response to growth factor stimulus / regulation of skeletal muscle contraction / syntrophin complex / synaptic signaling / cardiac muscle cell action potential / regulation of voltage-gated calcium channel activity / negative regulation of peptidyl-cysteine S-nitrosylation / positive regulation of sodium ion transmembrane transporter activity / dystrophin-associated glycoprotein complex ...regulation of muscle system process / regulation of cellular response to growth factor stimulus / regulation of skeletal muscle contraction / syntrophin complex / synaptic signaling / cardiac muscle cell action potential / regulation of voltage-gated calcium channel activity / negative regulation of peptidyl-cysteine S-nitrosylation / positive regulation of sodium ion transmembrane transporter activity / dystrophin-associated glycoprotein complex / regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion / peptide biosynthetic process / cell-substrate junction / motile cilium assembly / dystroglycan binding / vinculin binding / muscle cell development / costamere / neuron projection terminus / Striated Muscle Contraction / filopodium membrane / muscle organ development / structural constituent of muscle / muscle cell cellular homeostasis / maintenance of blood-brain barrier / myosin binding / nitric-oxide synthase binding / Non-integrin membrane-ECM interactions / neuron development / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / negative regulation of peptidyl-serine phosphorylation / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cardiac muscle contraction / skeletal muscle tissue development / regulation of ryanodine-sensitive calcium-release channel activity / response to muscle stretch / positive regulation of neuron differentiation / regulation of heart rate / filopodium / protein localization / structural constituent of cytoskeleton / 筋鞘 / positive regulation of neuron projection development / Z disc / actin binding / postsynaptic membrane / protein-containing complex assembly / 細胞骨格 / 脂質ラフト / シナプス / 細胞膜 / protein-containing complex / zinc ion binding / 細胞核 / 細胞膜 / 細胞質基質 類似検索 - 分子機能 |
生物種 | Homo sapiens (ヒト) |
引用 | ジャーナル: J Biol Chem / 年: 2018 タイトル: Dystrophin's central domain forms a complex filament that becomes disorganized by in-frame deletions. 著者: Olivier Delalande / Anne-Elisabeth Molza / Raphael Dos Santos Morais / Angélique Chéron / Émeline Pollet / Céline Raguenes-Nicol / Christophe Tascon / Emmanuel Giudice / Marine Guilbaud / ...著者: Olivier Delalande / Anne-Elisabeth Molza / Raphael Dos Santos Morais / Angélique Chéron / Émeline Pollet / Céline Raguenes-Nicol / Christophe Tascon / Emmanuel Giudice / Marine Guilbaud / Aurélie Nicolas / Arnaud Bondon / France Leturcq / Nicolas Férey / Marc Baaden / Javier Perez / Pierre Roblin / France Piétri-Rouxel / Jean-François Hubert / Mirjam Czjzek / Elisabeth Le Rumeur / 要旨: Dystrophin, encoded by the gene, is critical for maintaining plasma membrane integrity during muscle contraction events. Mutations in the gene disrupting the reading frame prevent dystrophin ...Dystrophin, encoded by the gene, is critical for maintaining plasma membrane integrity during muscle contraction events. Mutations in the gene disrupting the reading frame prevent dystrophin production and result in severe Duchenne muscular dystrophy (DMD); in-frame internal deletions allow production of partly functional internally deleted dystrophin and result in less severe Becker muscular dystrophy (BMD). Many known BMD deletions occur in dystrophin's central domain, generally considered to be a monotonous rod-shaped domain based on the knowledge of spectrin family proteins. However, the effects caused by these deletions, ranging from asymptomatic to severe BMD, argue against the central domain serving only as a featureless scaffold. We undertook structural studies combining small-angle X-ray scattering and molecular modeling in an effort to uncover the structure of the central domain, as dystrophin has been refractory to characterization. We show that this domain appears to be a tortuous and complex filament that is profoundly disorganized by the most severe BMD deletion (loss of exons 45-47). Despite the preservation of large parts of the binding site for neuronal nitric oxide synthase (nNOS) in this deletion, computational approaches failed to recreate the association of dystrophin with nNOS. This observation is in agreement with a strong decrease of nNOS immunolocalization in muscle biopsies, a parameter related to the severity of BMD phenotypes. The structural description of the whole dystrophin central domain we present here is a first necessary step to improve the design of microdystrophin constructs toward the goal of a successful gene therapy for DMD. |
登録者 |
|
-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
---|
-ダウンロードとリンク
-モデル
モデル #437 | タイプ: atomic / ダミー原子の半径: 1.90 A / カイ2乗値: 62.7264 Omokage検索でこの集合体の類似形状データを探す (詳細) |
---|
-試料
試料 | 名称: Human dystrophin central domain repeats 16 to 17 |
---|---|
バッファ | 名称: 20 mM Tris 150 mM NaCl 1 mM EDTA 2% glycerol / 濃度: 20.00 mM / pH: 7.5 / 組成: 150 mM NaCl, 1 mM EDTA, 2% glycerol |
要素 #288 | 名称: Dystrophin 1984-2216 / タイプ: protein / 記述: Dystrophin central domain repeats 16 to 17. / 分子量: 27.681 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: P11532 配列: GSvmtedmpl eisyvpstyl teithvsqal leveqllnap dlcakdfedl fkqeeslkni kdslqqssgr idiihskkta alqsatpver vklqealsql dfqwekvnkm ykdrqgrfdr svekwrrfhy dikifnqwlt eaeqflrktq ipenwehaky kwylkelqdg ...配列: GSvmtedmpl eisyvpstyl teithvsqal leveqllnap dlcakdfedl fkqeeslkni kdslqqssgr idiihskkta alqsatpver vklqealsql dfqwekvnkm ykdrqgrfdr svekwrrfhy dikifnqwlt eaeqflrktq ipenwehaky kwylkelqdg igqrqtvvrt lnatgeeiiq qssktdasil qeklgslnlr wqevckqlsd rkkrleeqkn ilsef |
-実験情報
ビーム | 設備名称: SOLEIL SWING / 地域: Saint-Aubin / 国: France / 線源: X-ray synchrotronシンクロトロン / 波長: 0.1 Å / スペクトロメータ・検出器間距離: 1.82 mm | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
検出器 | 名称: AVIEX / タイプ: CCD | ||||||||||||||||||
スキャン | タイトル: Human dystrophin central domain repeats 16 to 17 測定日: 2012年9月19日 / 保管温度: 15 °C / 照射時間: 1.5 sec. / フレーム数: 20 / 単位: 1/nm /
| ||||||||||||||||||
距離分布関数 P(R) | ソフトウェア P(R): GNOM 4.6 / ポイント数: 271 /
| ||||||||||||||||||
結果 | D max: 13 / カーブのタイプ: single_conc /
|