SASDBB3: Human dystrophin central domain single repeat 23 (Dystrophin cent...

基本情報

• 登録情報: データベース: SASBDB / ID: SASDBB3

試料

Human dystrophin central domain single repeat 23

• Dystrophin central domain single repeat 23 (protein), Dystrophin 2800-2939, Homo sapiens

機能・相同性

分子機能:

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 / motile cilium assembly / peptide biosynthetic process / regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion / dystroglycan binding / vinculin binding / muscle cell development / costamere / neuron projection terminus / Striated Muscle Contraction / filopodium membrane / structural constituent of muscle / muscle organ development / myosin binding / muscle cell cellular homeostasis / maintenance of blood-brain barrier / nitric-oxide synthase binding / negative regulation of peptidyl-serine phosphorylation / Non-integrin membrane-ECM interactions / neuron development / regulation of ryanodine-sensitive calcium-release channel activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / cardiac muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / skeletal muscle tissue development / response to muscle stretch / positive regulation of neuron differentiation / regulation of heart rate / filopodium / sarcolemma / structural constituent of cytoskeleton / 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

ドメイン・相同性:

Dystrophin/utrophin / EF-hand domain, type 1 / EF-hand domain, type 2 / : / EF hand / EF-hand / Spectrin repeat / Spectrin repeat / Spectrin/alpha-actinin / Spectrin repeats / Actinin-type actin-binding domain signature 1. / Actinin-type actin-binding domain signature 2. / Actinin-type actin-binding domain, conserved site / Calponin homology domain / Zinc finger ZZ-type signature. / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Calponin homology (CH) domain / Zinc finger, ZZ type / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / Calponin homology domain / CH domain superfamily / Calponin homology (CH) domain profile. / WW domain / WW/rsp5/WWP domain signature. / WW domain superfamily / WW/rsp5/WWP domain profile. / Domain with 2 conserved Trp (W) residues / WW domain / EF-hand domain pair

構成要素:

Dystrophin

• 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 / 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 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

• Elisabeth Le Rumeur (Université de Rennes 1, Institut Génétique et Développement de Rennes, France)

モデル

• モデル #440: ; タイプ: atomic / ダミー原子の半径: 1.90 A; 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 single repeat 23
• 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 #291

名称: Dystrophin 2800-2939 / タイプ: protein / 記述: Dystrophin central domain single repeat 23 / 分子量: 16.537 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: P11532
配列:

GSLEASSDQW KRLHLSLQEL LVWLQKDDEL SRQAPIGGDF PAVQKQNDVH RAFKRELKTK EPVIMSTLET VRIFLTEQPL EGLEKLYQEP RELPPEERAQ NVTRLLRKQA EEVNTEWEKL NLHSADWQRK IDETLERLQE

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 PCCD170170 / タイプ: CCD

スキャン

タイトル: Human dystrophin central domain single repeat 23
測定日: 2011年10月7日 / 保管温度: 15 °C / 照射時間: 1.5 sec. / フレーム数: 30 / 単位: 1/nm /

	Min	Max
Q	0.0504	5.392

距離分布関数 P(R)

ソフトウェア P(R): GNOM 4.6 / ポイント数: 476 /

	Min	Max
Q	0.009576	0.2488
P(R) point	10	485
R	0	74

結果

D max: 7.4 / カーブのタイプ: single_conc /

	実験値	Porod
分子量	12.5 kDa	12.5 kDa
体積	-	20 nm3

	P(R)	Guinier
前方散乱 I0	0.0351	0.0353
慣性半径, Rg	2.2 nm	2.2 nm