STRUCTURAL STUDIES OF CALRETICULIN AND SACSIN

钙网蛋白和 SACSIN 的结构研究

• 批准号: 8363536
• 负责人: Kalle B Gehring
• 金额: $ 2.99万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363536
• 关键词: Ataxia; Binding; Binding Sites; Calnexin; Canada; Cell physiology; Endoplasmic Reticulum; Funding; Genes; Glycoproteins; Grant; High Prevalence; Homologous Gene; Lectin; Membrane Proteins; Molecular Chaperones; N-terminal; National Center for Research Resources; Neurodegenerative Disorders; Principal Investigator; Process; Proline-Rich Domain; Proteins; Quebec; Research; Research Infrastructure; Resources; Role; Saints; Source; Spastic; Structure; Ubiquitin; United States National Institutes of Health; calreticulin; cost; early onset; insight; polypeptide; protein function; sacsin; secretory protein

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The calnexin cycle is a cellular process when secretory proteins are translocated into the lumen of the endoplasmic reticulum (ER) to become N-glycosylated and folded. The control components of the process are the membrane protein calnexin (CNX) and its soluble homologue calreticulin (CRT) that selectively recognize glycoproteins. CRT consists of a globular lectin-like domain, a hairpin-like proline-rich domain and an unstructured C-terminus rich in acidic residues. Recent studies suggest that CRT also functions as a chaperone by directly binding hydrophobic polypeptides via binding site in the globular domain. Here, we crystallized the globular domain of calreticulin. The structure will help to identify residues involved in glycoprotein binding and chaperoning activities. Autosomal recessive spastic ataxia of CharlevoixSaguenay (SACS) is an early-onset neurodegenerative disease with high prevalence in the CharlevoixSaguenayLac-Saint-Jean region of Quebec (Canada). The gene responsible for ARSACS produces a single protein SACSIN (4579 aa, MW=520 kDa). The function of the protein is unknown. The N-terminal part of the protein contains a domain with weak sequence similarity to ubiquitin-like (UBL) domains. The structure will provide insights into functional role of SACSIN.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 钙联蛋白循环是分泌蛋白易位至内质网 (ER) 腔内进行 N-糖基化并折叠的细胞过程。该过程的控制成分是膜蛋白钙联蛋白 (CNX) 及其可选择性识别糖蛋白的可溶性同系物钙网蛋白 (CRT)。 CRT 由球状凝集素样结构域、发夹样富含脯氨酸的结构域和富含酸性残基的非结构化 C 末端组成。最近的研究表明，CRT 还可以通过球状结构域中的结合位点直接结合疏水性多肽，从而起到伴侣的作用。在这里，我们结晶了钙网蛋白的球状结构域。该结构将有助于识别参与糖蛋白结合和陪伴活动的残基。 夏洛瓦萨格奈常染色体隐性痉挛性共济失调 (SACS) 是一种早发性神经退行性疾病，在加拿大魁北克省夏洛瓦萨格奈 Lac-Saint-Jean 地区患病率很高。负责 ARSACS 的基因产生单一蛋白质 SACSIN（4579 个氨基酸，MW=520 kDa）。该蛋白质的功能尚不清楚。该蛋白的 N 末端部分包含一个与泛素样 (UBL) 结构域具有弱序列相似性的结构域。该结构将提供对 SACSIN 功能作用的深入了解。