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データを開く
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基本情報
登録情報 | データベース: SASBDB / ID: SASDBV3 |
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![]() | Dystrophin central domain repeats 16 to 21 (Δ2146-2305; Becker muscular dystrophy variant)
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機能・相同性 | ![]() 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 / negative regulation of peptidyl-serine phosphorylation / Non-integrin membrane-ECM interactions / 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 / 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 / sarcolemma / positive regulation of neuron projection development / Z disc / 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 |
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![]() | ![]() 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. |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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-モデル
モデル #488 | ![]() タイプ: dummy / ダミー原子の半径: 1.90 A / カイ2乗値: 2.3409 / P-value: 0.000500 ![]() |
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試料
![]() | 名称: Dystrophin central domain repeats 16 to 21 (Δ2146-2305; Becker muscular dystrophy variant) 試料濃度: 5 mg/ml |
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バッファ | 名称: 20 mM Tris 150 mM NaCl 1 mM EDTA 2% glycerol 5% acetonitrile 濃度: 20.00 mM / pH: 7.5 組成: 150 mM NaCl, 1 mM EDTA, 2% glycerol, 5% acetonitrile |
要素 #309 | 名称: Dystrophin1991-2694Δ / タイプ: protein 記述: Dystrophin central domain repeats 16 to 21 (Δ2146-2305; Becker muscular dystrophy variant, deletion of exons 45-47) 分子量: 63.894 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: P11532 配列: GSleisyvps tylteithvs qalleveqll napdlcakdf edlfkqeesl knikdslqqs sgridiihsk ktaalqsatp vervklqeal sqldfqwekv nkmykdrqgr fdrsvekwrr fhydikifnq wlteaeqflr ktqipenweh akykwylkvs ralpekqgei ...配列: GSleisyvps tylteithvs qalleveqll napdlcakdf edlfkqeesl knikdslqqs sgridiihsk ktaalqsatp vervklqeal sqldfqwekv nkmykdrqgr fdrsvekwrr fhydikifnq wlteaeqflr ktqipenweh akykwylkvs ralpekqgei eaqikdlgql ekkledleeq lnhlllwlsp irnqleiynq pnqegpfdvq eteiavqakq pdveeilskg qhlykekpat qpvkrkledl ssewkavnrl lqelrakqpd lapglttiga sptqtvtlvt qpvvtketai sklempsslm levpaladfn rawteltdwl slldqviksq rvmvgdledi nemiikqkat mqdleqrrpq leelitaaqn lknktsnqea rtiitdrier iqnqwdevqe hlqnrrqqln emlkdstqwl eakeeaeqvl gqaraklesw kegpytvdai qkkitetkql akdlrqwqtn vdvandlalk llrdysaddt rkvhmiteni naswrsihkr vsereaalee thrllqqf |
-実験情報
ビーム | 設備名称: SOLEIL SWING ![]() ![]() | |||||||||||||||||||||||||||
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検出器 | 名称: AVIEX / タイプ: CCD | |||||||||||||||||||||||||||
スキャン | 測定日: 2014年2月5日 / 保管温度: 15 °C / 照射時間: 1.5 sec. / フレーム数: 21 / 単位: 1/nm /
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距離分布関数 P(R) |
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結果 |
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