Structure and function of cytochrome b561

描述（由申请方提供）：肾上腺抗坏血酸依赖性细胞色素（cyt.）B561是合成儿茶酚胺和某些肽激素所需的跨膜电子转运蛋白，并且是扩增的且未充分表征的细胞色素的原型。b561蛋白家族;其他哺乳动物家族成员与肠道铁转运和肿瘤抑制有关。我们的总体目标是描述肾上腺b561的机制，并利用有关这种细胞色素的信息来了解其他b561家族成员的结构和功能。本课题的具体目标是：1）明确肾上腺细胞的结构核心。b561，确定其与细胞膜双分子层的关系，并评估其在哺乳动物细胞色素细胞中的通用性。b561家族成员; 2）肾上腺细胞相互作用的特征。b561与其天然还原剂抗坏血酸盐及其天然氧化剂半氢化抗坏血酸盐;和3）确定通过肾上腺细胞的电子流路径。第561章和他的约定将对天然哺乳动物蛋白和重组野生型和突变型肾上腺细胞色素和其他哺乳动物细胞色素进行计划的实验。b561家族成员在原核和真核系统，我们已经开发。我们将利用生物化学和生物物理学技术来表征这些重组蛋白和纯化的内源性肾上腺细胞色素b561的拓扑学、结构和动力学特性。了解肾上腺细胞。B561的功能是理解人体中肾上腺素和去甲肾上腺素以及某些肽激素的生理学和病理学的基本部分。确定肾上腺细胞之间的相似性和差异。b561和最近发现的人cyt。B561家族成员将加速对较新的Cyt的生理和病理作用的表征。b561型。

DESCRIPTION (provided by applicant): Adrenal ascorbate-dependent cytochrome (cyt.) b561 is a transmembrane electron transporter required for synthesis of catecholamine and some peptide hormone and is the prototype of an expanding and insufficiently characterized cyt. b561 protein family; other mammalian family members have been linked to intestinal iron transport and tumor suppression. Our overall goal is to characterize the mechanism of adrenal b561 and to use information about this cytochrome to understand the structure and function of other b561 family members. The specific aims of this project are: 1) Define the structural kernel of adrenal cyt. b561, determine its relationship to the membrane bilayer, and evaluate the kernel's generality among mammalian cyt. b561 family members; 2) Characterize the interaction of adrenal cyt. b561 with its natural reductant, ascorbate, and its natural oxidant, semidehydroascorbate; and 3) Determine the path of electron flow via adrenal cyt. b561 and its regulation. Planned experiments will be conducted on the native mammalian protein and recombinant wild type and mutant forms of the adrenal cytochrome and other mammalian cyt. b561 family members in prokaryotic and eukaryotic systems that we have developed. We will characterize the topological, structural, and kinetic properties of these recombinant proteins and purified endogenous adrenal cyt b561 using biochemical and biophysical techniques. Understanding how adrenal cyt. b561 functions is a fundamental part of understanding the physiology and pathology of epinephrine and norepinephrine and of some peptide hormones in humans. Defining similarities and differences between adrenal cyt. b561 and recently-discovered human cyt. b561 family members will accelerate characterization of the physiological and pathological roles of the newer cyt. b561s.