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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 当将分泌蛋白易位到内质网（ER）的腔内以成为N-糖基化并折叠时，钙钙蛋白周期是一种细胞过程。该过程的控制成分是膜蛋白钙钙蛋白（CNX）及其可溶性同源钙网蛋白（CRT），可有选择地识别糖蛋白。 CRT由一个球状凝集素样结构域，一个富含发夹的脯氨酸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还通过直接通过球状结构域中的结合位点结合疏水性多肽来充当伴侣。在这里，我们结晶了钙网蛋白的球状结构域。该结构将有助于确定涉及糖蛋白结合和伴侣活动的残基。 Charlevoix Saguenay（SACS）的常染色体隐性痉挛性共济失调是一种早期发作的神经退行性疾病，在加拿大魁北克（加拿大）的Charlevoix Saguenay Lac-Saint-Jean地区，患病率很高。负责ARSAC的基因产生单个蛋白囊蛋白（4579 AA，MW = 520 kDa）。蛋白质的功能未知。该蛋白质的N末端部分包含一个与泛素样（UBL）结构域具有较弱序列相似性的结构域。该结构将提供有关Sacsin功能作用的见解。