COTRANSLATIONAL PROCESSING AND PROTEIN TURNOVER
共翻译加工和蛋白质周转
基本信息
- 批准号:2701065
- 负责人:
- 金额:$ 22.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-09-30 至 2002-06-30
- 项目状态:已结题
- 来源:
- 关键词:active sites acyltransferase aminohydrolases aminopeptidase cell growth regulation chimeric proteins confocal scanning microscopy enzyme activity enzyme mechanism enzyme structure enzyme substrate fungal genetics glycosylation immunoaffinity chromatography immunoprecipitation isozymes matrix assisted laser desorption ionization methionine molecular cloning posttranslational modifications protein degradation protein localization protein sequence site directed mutagenesis ubiquitin
项目摘要
DESCRIPTION: (Adapted from the application) N-terminal processing of
proteins in eukaryotes occurs both co- and post-translationally and the
resulting modifications are involved in translocation, regulation of
activity and turnover. The initial reactions involve the removal of the
initiator methionine and the addition of N-alpha acetyl groups by
methionine aminopeptidases (Met AP) and N-alpha-acetyl transferases (NAT),
respectively. Each exists in multiple isoforms that appear to differ in
specificity, regulation of cellular location. Using recombinant material,
the role of the two types of yeast MetAPs will be determined and the
proteins characterized with respect to structural and functional
properties, including metal content, substrate specificity and catalytic
organization. Site-directed mutagenesis and chemical inhibitors will be
extensively used. Cellular localization will also be determined with
recombinant fusion proteins and immunological reagents. Recombinant human
isoforms will also be prepared and examined for putative glycosylations
and the role of the type II enzyme in cell cycle regulation. Similar
studies will be carried out with the NATs, with a focus on the subforms
specific for N-terminal Met (produced by penultimate Asp, Glu and Asn-the
"DEN" subset). In parallel to the NATs that modify the Gly, Ala, Ser, and
Thr (GAST) group, the M-NATs exist as a pair of proteins that may
functions as a heterodimer complex. This hypothesis will be tested as a
part of the structural characterizations. Two enzymes putatively involved
in downstream processing of DEN proteins that will also be investigated.
In the first case, yeast will be screened (and enzyme isolated if
detected) for an acyl amino acid hydrolase, specific for acetyl Met
groups, that could destabilize DEN proteins for degradation by the N-end
Rule. In the second, human protein N-terminal asparagine amidohydrolase,
which converts N-terminal Asn residues to Asp (the yeast form also acts on
Gln), will be isolated and further characterized. Finally, yeast null
strains, deficient in several of these (and other) co-/post-
translationally active enzymes, will be used to confirm their putative
physiological roles and to identify proteins degraded in an N-terminal
specific manner.
描述:(改编自应用程序)N-末端处理
真核生物中的蛋白质既发生在协同作用下,也发生在协同作用后,
由此产生的修饰涉及易位,调节
活动和营业额。最初的反应包括去除
引发剂甲硫氨酸和N-α乙酰基的加成,
甲硫氨酸氨基肽酶(Met AP)和N-α-乙酰基转移酶(NAT),
分别每一种都存在于多个亚型中,这些亚型在
特异性,细胞定位的调节。使用重组材料,
两种类型的酵母MetAP的作用将被确定,
蛋白质的结构和功能特征
性质,包括金属含量、底物特异性和催化性
organization.定点诱变和化学抑制剂将被
广泛使用。细胞定位也将通过
重组融合蛋白和免疫学试剂。重组人
还将制备同种型并检查推定的糖基化
以及II型酶在细胞周期调节中的作用。类似
将与NATs一起进行研究,重点是子形式
特异于N-末端Met(由倒数第二个Asp、Glu和Asn产生),
“DEN”子集)。与修饰Gly、Ala、Ser和
Thr(GAST)组,M-NAT作为一对蛋白质存在,
作为异二聚体复合物起作用。这一假设将作为一个
部分结构特征。涉及两种酶
在DEN蛋白的下游加工中也将被研究。
在第一种情况下,将筛选酵母(如果需要,则分离酶)。
检测)的酰基氨基酸水解酶,特异于乙酰Met
基团,其可以使DEN蛋白不稳定以通过N-末端降解
统治在第二,人蛋白N-末端天冬酰胺水解酶,
其将N-末端Asn残基转化为Asp(酵母形式也作用于
Gln),将被分离并进一步表征。最后,酵母空
这些(和其他)共同/后-
将用于确认其推定的
生理作用,并鉴定N-末端降解的蛋白质
具体方式。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RALPH A BRADSHAW其他文献
RALPH A BRADSHAW的其他文献
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{{ truncateString('RALPH A BRADSHAW', 18)}}的其他基金
MOLECULAR ANALYSIS OF FIBROBLAST GROWTH FACTOR RECEPTOR 3 MUTATIONS
成纤维细胞生长因子受体 3 突变的分子分析
- 批准号:
6410469 - 财政年份:2000
- 资助金额:
$ 22.96万 - 项目类别:
MOLECULAR ANALYSIS OF FIBROBLAST GROWTH FACTOR RECEPTOR 3 MUTATIONS
成纤维细胞生长因子受体 3 突变的分子分析
- 批准号:
6301930 - 财政年份:1999
- 资助金额:
$ 22.96万 - 项目类别:
MOLECULAR ANALYSIS OF FIBROBLAST GROWTH FACTOR RECEPTOR 3 MUTATIONS
成纤维细胞生长因子受体 3 突变的分子分析
- 批准号:
6108480 - 财政年份:1998
- 资助金额:
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ASBMB FALL SYMPOSIUM REGULATION OF BONE FORMATION
ASBMB 秋季研讨会骨形成的调节
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2796260 - 财政年份:1998
- 资助金额:
$ 22.96万 - 项目类别:
MOLECULAR ANALYSIS OF FIBROBLAST GROWTH FACTOR RECEPTOR 3 MUTATIONS
成纤维细胞生长因子受体 3 突变的分子分析
- 批准号:
6272129 - 财政年份:1997
- 资助金额:
$ 22.96万 - 项目类别:
MOLECULAR ANALYSIS OF FIBROBLAST GROWTH FACTOR RECEPTOR 3 MUTATIONS
成纤维细胞生长因子受体 3 突变的分子分析
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6241029 - 财政年份:1996
- 资助金额:
$ 22.96万 - 项目类别:
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