+データを開く
-基本情報
登録情報 | データベース: SASBDB / ID: SASDB43 |
---|---|
試料 | Human dystrophin central domain repeats 1 to 2
|
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 / regulation of voltage-gated calcium channel activity / negative regulation of peptidyl-cysteine S-nitrosylation / cardiac muscle cell action potential / 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 / regulation of voltage-gated calcium channel activity / negative regulation of peptidyl-cysteine S-nitrosylation / cardiac muscle cell action potential / positive regulation of sodium ion transmembrane transporter activity / dystrophin-associated glycoprotein complex / cell-substrate junction / peptide biosynthetic process / motile cilium assembly / dystroglycan binding / regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion / 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 / myosin binding / maintenance of blood-brain barrier / nitric-oxide synthase binding / negative regulation of peptidyl-serine phosphorylation / Non-integrin membrane-ECM interactions / regulation of ryanodine-sensitive calcium-release channel activity / neuron development / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cardiac muscle contraction / skeletal muscle tissue development / response to muscle stretch / positive regulation of neuron differentiation / regulation of heart rate / filopodium / structural constituent of cytoskeleton / sarcolemma / Z disc / positive regulation of neuron projection development / protein localization / actin binding / protein-containing complex assembly / postsynaptic membrane / cytoskeleton / membrane raft / synapse / cell surface / protein-containing complex / zinc ion binding / nucleus / plasma membrane / cytosol 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 #433 | タイプ: atomic / ダミー原子の半径: 1.90 A / カイ2乗値: 5.673924 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 1 to 2 |
---|---|
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 #284 | 名称: Dystrophin 338-563 / タイプ: protein / 記述: Dystrophin central domain repeats 1 to 2 / 分子量: 26.367 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: P11532 配列: GSEVNLDRYQ TALEEVLSWL LSAEDTLQAQ GEISNDVEVV KDQFHTHEGY MMDLTAHQGR VGNILQLGSK LIGTGKLSED EETEVQEQMN LLNSRWECLR VASMEKQSNL HRVLMDLQNQ KLKELNDWLT KTEERTRKME EEPLGPDLED LKRQVQQHKV LQEDLEQEQV ...配列: GSEVNLDRYQ TALEEVLSWL LSAEDTLQAQ GEISNDVEVV KDQFHTHEGY MMDLTAHQGR VGNILQLGSK LIGTGKLSED EETEVQEQMN LLNSRWECLR VASMEKQSNL HRVLMDLQNQ KLKELNDWLT KTEERTRKME EEPLGPDLED LKRQVQQHKV LQEDLEQEQV RVNSLTHMVV VVDESSGDHA TAALEEQLKV LGDRWANICR WTEDRWVLLQ DILLKWQR |
-実験情報
ビーム | 設備名称: SOLEIL SWING / 地域: Saint-Aubin / 国: France / 線源: X-ray synchrotron / 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 1 to 2 測定日: 2011年10月7日 / 保管温度: 15 °C / 照射時間: 1.5 sec. / 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: 338 /
| ||||||||||||||||||
結果 | D max: 10.6 / カーブのタイプ: single_conc /
|