EPIDERMAL TRANSGLUTAMINASES

表皮谷氨酰胺转胺酶

• 批准号: 6160823
• 负责人: P STEINERT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160823
• 关键词: active sites; crosslink; enzyme activity; enzyme mechanism; genetic promoter element; human tissue; isozymes; keratinocyte; lysine; membrane proteins; membrane structure; protein glutamine gamma glutamyltransferase; protein structure function; skin; solubility; tissue /cell culture

Transglutaminases form an isopeptide crosslink between an donor amide group of a protein-bound glutamine residue and a acceptor epsilon-NH2 of a protein-bound lysine residue, thereby forming an insoluble macromolecular protein complex. In the epidermis, at least three enzymes are thought to function by crosslinking certain defined structural proteins to form the cornified cell envelope, and are transglutaminases 1, 2 and 3. We are studying these enzymes in detail. The transglutaminase 1 enzyme in cultured keratinocytes or foreskin epidermal cells is complex, since it exists in multiple soluble and membrane-bound full-length as well as proteolytically-processed forms. The partitioning between the cytosol and membranes is controlled by differential acylation by myristate and palmitate. The enzyme is widely expressed in the epidermis and appendageal structures, as well as in other non-epithelial tissues. Similarly, the transglutaminase 3 enzyme is expressed in many other non-epithelial cell types. The proximal promoter region of the transglutaminase 3 gene is located within the first 126 bp above the transcription start site, and consists of an Sp1 motif modulated by adjacent ets-like motifs. These are sufficient to confer epithelial-specific expression. This region also contains a calcium responsive element. Crystallographic structural studies on each of the three enzymes are in progress.

转氨酶在供体酰胺与供体酰胺之间形成异肽交联， 蛋白质结合的谷氨酰胺残基和受体ε-NH 2的基团 与蛋白质结合的赖氨酸残基，从而形成不溶的 大分子蛋白质复合物 在表皮中，至少有三种酶 被认为是通过交联某些定义的结构 形成皮质细胞被膜的蛋白质，是转氨酶 1、2和3。 我们正在详细研究这些酶。 的 培养的角质形成细胞或包皮表皮中的转氨酶1酶 细胞是复杂的，因为它存在于多个可溶性和膜结合 全长以及蛋白水解加工的形式。 分隔 细胞质和细胞膜之间的相互作用是由不同的酰化作用控制的 肉豆蔻酸酯和棕榈酸酯 这种酶在大肠杆菌中广泛表达， 表皮和附件结构，以及其他非上皮 组织中 类似地，转氨酶3酶在许多细胞中表达。 其他非上皮细胞类型。 基因的近端启动子区 转氨酶3基因位于第一个126 bp以上， 转录起始位点，由Sp1基序组成， 相邻的类ETS基序。 这些足以使 上皮特异性表达。 该区域还含有钙 响应元件 晶体结构研究表明， 三种酶正在进行中。