OPTICAL BIOSENSOR TO STUDY MACROMOLECULE INTERACTIONS

描述了一种将用于定义大分子之间相互作用的生物传感器仪器的特性和能力。它的收购将建立一系列用于这一目的的工具之一。该提案是由七名研究人员提交的，他们参与了蛋白质-蛋白质、配体-蛋白质、肽-蛋白质或蛋白质-膜相互作用的研究，他们在高分辨率蛋白质结构研究以及生物化学、生物物理学和分子遗传学领域拥有专业知识。生物传感器仪器将补充和扩展从高分辨率结构研究中获得的信息，提供关于蛋白质功能和机制的信息。将解决一系列广泛的问题。这些包括：(I)膜活性蛋白的膜结合亲和力的性质；(Ii)粘附素与其细胞受体的相互作用；(Iii)抗人鼻病毒抗体的结合亲和力；(Iv)肠毒素的受体相互作用；(V)亚洲酒精脱氢酶改变NAD+的结合；(Vi)线粒体前导肽与其受体的结合；(Vii)G蛋白受体与小窝蛋白的相互作用；(Viii)红细胞带III肽与糖酵解酶以及赖氨酸激酶和B细胞抗原受体的相互作用；(Ix)SH2介导的P72-SYK和src-家族激酶lck之间的相互作用；(X)profilin-actin相互作用及其被富含Pro的蛋白质和磷脂酰肌醇等配体的调节。

The properties and capabilities are described of a biosensor instrument that will be used to define interactions between macromolecules. Its acquisition would establish one of an array of instruments to be used for this purpose. The proposal is submitted by seven investigators involved in studies on protein-protein, ligand-protein, peptide-protein, or protein-membrane interactions, who have expertise in high resolution protein structure studies, and in areas of biochemistry, biophysics, and molecular genetics. The biosensor instrumentation would complement and extend the information obtained from the high resolution structure studies by providing information on protein function and mechanism. A wide range of problems will be addressed. These include: (i) the nature of the membrane binding affinity of "membrane-active" proteins; (ii) the interaction between colicins and their cellular receptor; (iii) the binding affinity of antibodies to human rhinovirus; (iv) receptor interactions of enterotoxins; (v) altered binding of NAD+ by Asian alcohol dehydrogenase; (vi) binding of mitochondrial leader peptides to their receptors; (vii) interaction of G protein receptors with caveolin; (viii) interactions of erythrocyte band III peptide with glycolytic enzymes, and of lyn tyrosine kinase and B-cell antigen receptor; (ix) SH2-mediated interactions between p72 syk and the src-family kinase lck; (x) profilin-actin interactions and their modulation by ligands including proline-rich proteins and phosphoinositide lipids.