CALMODULIN TARGET PROTEINS; STRUCTURE-FUNCTION RELATIONSHIPS

钙调蛋白靶蛋白；

• 批准号: 7601295
• 负责人: ALLEN R RHOADS
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601295
• 关键词: ATP phosphohydrolase; Adenylate Cyclase; Affinity; Age; Amino Acid Motifs; Amino Acid Sequence; Binding; Binding Proteins; Binding Sites; Bordetella pertussis; Calcineurin; Calcium; Calmodulin; Class; Computer Retrieval of Information on Scientific Projects Database; Databases; EF Hand Motifs; Enzymes; Evolution; Family; Funding; Genes; Genome; Glycogen Phosphorylase; Grant; Growth Associated Protein 43; Institution; Lithium; Lung; Molecular; Myosin Light Chain Kinase; Nitric Oxide Synthase; Nucleotides; Peptide Sequence Determination; Phosphorylase Kinase; Phosphorylation Site; Phylogenetic Analysis; Positioning Attribute; Procedures; Protein Binding; Protein Dynamics; Proteins; Pseudogenes; Psychiatry; Publications; Pump; Radiation Hybrid Map; Radiation Hybrid Mapping; Relative (related person); Research; Research Personnel; Resources; Signal Pathway; Source; Structure; Structure-Activity Relationship; Taxon; Trace Elements; United States National Institutes of Health; calcium-dependent protein kinase; caldesmon; fodrin; macrophage; myristoylated alanine-rich C kinase substrate; neurogranin; phosphoric diester hydrolase; programs; protein structure function

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 research plan involves examining the different families of calmodulin-dependent proteins to determine: (1) structural or functional binding motifs of calmodulin(CAM) and the position of phosphorylation sites or pseudosubstrate domains or homologous regions relative to the CAM-binding domain; (2) comparison of EF-hand proteins in different eucaryotic genomes and tracing elements of their signaling pathways; (3) searching the database for sequences similar to regions associated with CAM binding and secondary structure prediction in the vicinity of the CAM-binding site; (4) examining the phylogenetic relationships and ages of divergence among taxa utilizing retroprocessed CAM pseudogenes as neutral markers of evolution (5) examination of local multiple alignments of CAM-binding proteins by dynamic programming procedures. Protein sequences investigated include the entire spectrum of CAM target proteins. The spectrum includes: Class 1 target proteins that bind to CAM without associated calcium and may have reduced affinity for calcium/CAM; Class 2 proteins that bind CAM strongly in the absence of calcium and may be positively activated by calcium; and the major Class 3 proteins that have high affinity for the calcium/CAM and are activated by it. Class 1 examples are neuromodulin, neurogranin and some IQ motif proteins. Class 2 are macrophage NO synthase, lung cyclic 3`, 5`-nucleotide phosphodiesterase, bordetella pertussis adenylate cyclase, and glycogen phosphorylase b kinase;and class 3 containing the enzymes and proteins such as calcineurin, myosin light chain kinase, caldesmon, adenylate cyclases, fodrin, MARCKS protein, adducins, protein kinases, calcium-dependent ATPase pumps and others. Publications - Rhoads, A.R. and Friedberg, F.: "Sequence Motifs for Calmodulin Recognition.": FASEB J. 11: 331-340: 1997; Rhoads, A.R., Karkera, J.D., and Detera-Wadleigh, S.D.: "Radiation Hybrid Mapping of Genes in the Lithium-Sensitive Wnt Signaling Pathway." : Molecular Psychiatry 4: 437-442: 1999; Friedberg, F. and Rhoads, A.R.: "Calculation and Verification of the Ages of Retroprocessed Pseudogenes.": Molecular Phylogenetics and Evolution: 16: 2000 (In Press);

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 研究计划包括检查钙调蛋白依赖性蛋白的不同家族，以确定：（1）钙调蛋白（CAM）的结构或功能结合基序以及磷酸化位点或假底物结构域或相对于CAM结合结构域的同源区域的位置； （2）不同真核生物基因组中EF-hand蛋白的比较及其信号通路的示踪元件； (3)在数据库中搜索与CAM结合相关区域相似的序列以及CAM结合位点附近的二级结构预测； (4) 利用逆处理的 CAM 假基因作为进化的中性标记，检查分类单元之间的系统发育关系和分化年龄。 (5) 通过动态编程程序检查 CAM 结合蛋白的局部多重比对。研究的蛋白质序列包括 CAM 靶蛋白的整个谱系。该谱包括： 1 类靶蛋白，与 CAM 结合但不与钙结合，并且对钙/CAM 的亲和力可能降低； 2 类蛋白质在没有钙的情况下与 CAM 牢固结合，并可能被钙积极激活；以及与钙/CAM 具有高亲和力并被其激活的主要 3 类蛋白质。第 1 类的例子是神经调节蛋白、神经颗粒蛋白和一些 IQ 基序蛋白。第2类是巨噬细胞NO合酶、肺环3`、5`-核苷酸磷酸二酯酶、百日咳博德特氏菌腺苷酸环化酶和糖原磷酸化酶b激酶；第3类包含酶和蛋白质，例如钙调神经磷酸酶、肌球蛋白轻链激酶、caldesmon、腺苷酸环化酶、胞质蛋白、MARCKS 蛋白、内收蛋白、蛋白激酶、钙依赖性 ATP 酶泵等。 出版物 - Rhoads, A.R.和 Friedberg, F.：“钙调蛋白识别的序列基序”。：FASEB J. 11：331-340：1997； Rhoads, A.R.、Karkera, J.D. 和 Detera-Wadleigh, S.D.：“锂敏感 Wnt 信号通路中基因的辐射混合作图”。 ：分子精神病学4：437-442：1999； Friedberg, F. 和 Rhoads, A.R.：“Retroprocessed Pseudogenes 年龄的计算和验证。”：分子系统发育和进化：16：2000（印刷中）；