STRUCTURAL STUDIES OF CALRETICULIN AND SACSIN

钙网蛋白和 SACSIN 的结构研究

• 批准号: 8171523
• 负责人: Kalle B Gehring
• 金额: $ 1.4万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171523
• 关键词: Ataxia; Binding; Binding Sites; Calnexin; Canada; Cell physiology; Computer Retrieval of Information on Scientific Projects Database; Endoplasmic Reticulum; Funding; Genes; Glycoproteins; Grant; High Prevalence; Homologous Gene; Institution; Lectin; Membrane Proteins; Molecular Chaperones; N-terminal; Neurodegenerative Disorders; Process; Proline-Rich Domain; Proteins; Quebec; Research; Research Personnel; Resources; Role; Saints; Source; Spastic; Structure; Ubiquitin; United States National Institutes of Health; calreticulin; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 Charlevoix¿¿"Saguenay (SACS) is an early-onset neurodegenerative disease with high prevalence in the Charlevoix¿¿"Saguenay¿¿"Lac-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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 钙粘蛋白循环是一个细胞过程，当分泌蛋白被转移到内质网(ER)的管腔内，变成N-糖基化和折叠。这一过程的控制成分是膜蛋白Calnexin(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由一个球状的凝集素样结构域、一个发夹状的富含脯氨酸的结构域和一个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与疏水性多肽结合，从而发挥伴侣作用。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性的残基。 常染色体隐性遗传性痉挛共济失调是一种早发性神经退行性疾病，在加拿大魁北克省夏洛伊斯圣让地区发病率很高。负责ARSACS的基因产生单一蛋白SACSIN(4579氨基酸，MW=520 kDa)。该蛋白的功能尚不清楚。该蛋白的N端含有一个与泛素样结构域具有弱序列相似性的结构域。该结构将为深入研究SACSIN的功能作用提供线索。