INSECT DIURETIC HORMONES--STRUCTURES AND FUNCTION

昆虫利尿激素——结构和功能

• 批准号: 2770985
• 负责人: DAVID Allan SCHOOLEY
• 金额: $ 18.36万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2770985
• 关键词: Hymenoptera; Insecta; Lepidoptera; X ray crystallography; computer simulation; conformation; corticotropin releasing factor; diuresis; enzyme linked immunosorbent assay; high performance liquid chromatography; hormone receptor; hormone regulation /control mechanism; immunocytochemistry; invertebrate hormone; laboratory rabbit; mass spectrometry; neuropeptide receptor; neuropeptides; protein structure function; receptor binding; scintillation spectrometry; site directed mutagenesis; urination

Insects have low pressure circulatory systems and require diuretic hormones to control production of urine by Malpighian tubules. We identified the first insect diuretic hormone (DH), Manduca sexta DH, in 1989. There are now ten members of this growing family of DH (four identified with prior funding), which are structurally homologous to the corticotropin releasing factor/sauvagine/urotensin I family of peptides. An extremely novel aspect of the sequences of the CRF-like DH is that they have homologous regions for the amino terminal half of the 30-46 residue sequence, and homology at the carboxyl terminus of the molecule but gaps are required in the middle of most sequences for good alignment of both termini. These gaps in the sequence should cause profound differences in the three dimensional conformation of the related insect DHs; curiously, all but three of the known CRF-like DH activate Malpighian tubules of Manduca sexta. We propose studies to isolate and identify CRF-like DH from Rhodnius prolixus, a vector of Chagas' disease, and two other insect species. We plan to do the work on R. prolixus in collaboration with Prof. Ian Orchard, U. of Toronto, as possession of this disease vector is strictly controlled in the US. We will also study the relative three dimensional conformation of members of this family of DH by computer modeling and by physico-chemical methods, hopefully including X-ray crystallography. We also hope to learn more about how M. sexta and DH, and other DH, interact with their receptors. We propose to determine exactly what part of the molecule activates the receptor, and to determine to what part of the receptor molecule M. sexta DH binds. Studies on this unique family of neuropeptides will provide information which may be of utility in designing small molecules with DH activity, potentially of great use for control of blood-sucking insects. Analogues of insect juvenile hormones (sesquiterpenoids) are currently in commercial use as extremely safe, specific insect control agents.

昆虫的循环系统压力较低，需要利尿剂 控制马氏小管产生尿液的激素。 我们 鉴定出第一种昆虫利尿激素（DH），Manduca sexta DH， 1989 年。这个不断壮大的 DH 大家庭现在有 10 名成员（其中 4 名是 与先前的资助确定），其在结构上与 促肾上腺皮质激素释放因子/sauvagine/尾加压素 I 肽家族。 CRF 样 DH 序列的一个极其新颖的方面是它们 30-46 残基的氨基末端一半具有同源区域 分子羧基末端的序列和同源性，但有间隙 大多数序列的中间都需要，以确保两者的良好比对 终点站。 序列中的这些间隙应该会导致显着的差异 相关昆虫DH的三维构象；奇怪的是， 除了三个已知的 CRF 样 DH 之外，所有这些都激活马氏小管 烟草天蛾。 我们提出研究来分离和鉴定 CRF 样 DH 来自Rhodnius prolixus（南美锥虫病的媒介）和另外两种昆虫 物种。 我们计划与以下机构合作开展 R. prolixus 的研究工作： 多伦多大学 Ian Orchard 教授表示，拥有这种疾病媒介是 在美国受到严格控制。 我们还将研究成员的相对三维构象 通过计算机建模和物理化学方法对这个 DH 家族进行研究， 希望包括 X 射线晶体学。 我们也希望能够了解更多 关于 M. sexta 和 DH 以及其他 DH 如何与其受体相互作用。 我们建议准确确定分子的哪一部分激活 受体，并确定受体分子的哪一部分 M. sexta DH 结合。 对这个独特的神经肽家族的研究将提供信息 这可能有助于设计具有 DH 活性的小分子， 对于控制吸血昆虫有很大的用途。 类似物 昆虫保幼激素（倍半萜类化合物）目前已投入商业化 用作极其安全的特定昆虫控制剂。