The Solution Structure of Clip Domains from Manduca sexta Prophenoloxidase Activating Proteinase-2

• Published in: Biochemistry (Easton) Vol. 46; no. 41; pp. 11431 - 11439
• Main Authors: Huang, Rudan, Lu, Zhiqiang, Dai, Huaien, Vander Velde, David, Prakash, Om, Jiang, Haobo
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.10.2007
• Subjects: Animals; Binding Sites; Hydrogen Bonding; Insect Proteins - chemistry; Insect Proteins - isolation & purification; Magnetic Resonance Spectroscopy; Manduca - enzymology; Peptide Fragments - chemistry; Serine Endopeptidases - chemistry; Serine Endopeptidases - isolation & purification; Solutions
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi7010724

Clip domains are structural modules found in arthropod serine proteinases and some proteolytically inactive homologues, which mediate extracellular signaling pathways of development and immunity. While little is known about their structures or functions, clip domains are proposed to be sites for interactions of proteinases with their activators, cofactors, and substrates. Here we report the solution structure of dual clip domains from Manduca sexta prophenoloxidase activating proteinase-2. Each domain adopts a new mixed α/β fold (a three-stranded antiparallel β-sheet flanked by two α-helices), and the architecture provides structural information on clip domains from a catalytically active proteinase for the first time. Examination of the structure in conjunction with a multiple sequence alignment of the clip domains from different groups suggests a substrate-binding site, a bacteria-interacting region, and a surface for specific interactions. In summary, our results provide insights into the structural basis of clip domain functions and this structure may represent the prototype of group-2 clip domains.