Comparative Modeling of Amoebapores and Granulysin Based on the NK-Lysin Structure Structural and Functional Implications
-
H. Bruhn
and M. Leippe
Abstract
Amoebapores, the pore-forming polypeptides of the protozoan parasite Entamoeba histolytica, and effector proteins of porcine and human lymphocytes, namely NK-lysin and granulysin, reveal a substantial sequence similiarity despite their enormous evolutionary distance. Moreover, all these polypeptides display antibacterial activity and are in higher concentrations cytolytic to eukaryotic cells. The recently solved NMR structure of NK-lysin enabled us to build the three dimensional structures of amoebapores and granulysin by comparative modeling. The generated models revealed the expected similarities, but also fundamental differences with respect to charge distribution, hydrophobicity and core packing. The combination of these structural properties and known biochemical data provides insight in the different membrane-interacting mechanisms of the proteins. For amoebapores, exposed hydrophobic grooves and a locally loosely packed protein core may allow a rearrangement of the protein and therefore may account for its ability to penetrate the target membrane and to form defined ion channels in planar lipid bilayers.
In contrast, the structural features of NK-lysin and granulysin appear to be suitable for a membrane-perturbing mode of action rather than for channel formation.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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- Autonomous Regulation in Mammalian Mitochondrial DNA Transcription
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- Chimeric Restriction Enzymes: What Is Next?
- Viroids with Hammerhead Ribozymes: Some Unique Structural and Functional Aspects with Respect to Other Members of the Group
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- Agonist-Stimulated Pathways of Calcium Signaling in Pancreatic Acinar Cells
- Some of the Early Events Underlying Th2. Cell Maturation and Susceptibility to Leishmania major Infection in BALB/c Mice
- Universal and Unique Features of Kinesin Motors: Insights from a Comparison of Fungal and Animal Conventional Kinesins
- Elementary Steps in Protein Folding
- Molecular Reaction Mechanisms of Proteins Monitored by Time-Resolved FTIR-Spectroscopy
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