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Jürgen Sühnel jsuehnel@fli-leibniz.de

- 2013 - 3D Structures of Biological Macromolecules Exercise: Membrane Proteins. Jürgen Sühnel jsuehnel@fli-leibniz.de. Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena Centre for Bioinformatics Jena / Germany.

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Jürgen Sühnel jsuehnel@fli-leibniz.de

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  1. - 2013 - 3D Structuresof Biological Macromolecules Exercise: Membrane Proteins Jürgen Sühnel jsuehnel@fli-leibniz.de Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena CentreforBioinformatics Jena / Germany Supplementary Material: http://www.fli-leibniz.de/www_bioc/3D/

  2. Cell Membrane

  3. Membrane Structural Components

  4. Lipids

  5. Cholesterol, a ConstituentoftheCell Membrane Without cholesterol, cell membranes would be too fluid, not firm enough, and too permeable to some molecules. In other words, it keeps the membrane from turning to mush. Cholesterol is an amphipathic molecule, meaning, like phospholipids, it contains a hydrophilic and a hydrophobic portion. Cholesterol's hydroxyl (OH) group aligns with the phosphate heads of the phospholipids. The remaining portion of it tucks into the fatty acid portion of the membrane.

  6. Membrane Proteins • Integral membrane proteins (penetrating the lipid bilayer; permanently attached) • [Insulin receptor, rhodopsin, …] • Integral polytopic membrane proteins (transmembrane proteins) • Integral monotopic membrane proteins • Peripheral membrane proteins (external bound with non-covalent bonds; temporarily attached) • [Enzymes: phospholipase …] • Lipid-anchored proteins (external bound with covalent bonds) • [G proteins …]

  7. Integral Polytopic Membrane (Transmembrane) Proteins • Schematicrepresentationoftransmembraneproteins: • a singletransmembraneα-helix (bitopicmembraneprotein) • a polytopictransmembraneα-helicalprotein • a polytopictransmembraneβ-sheetprotein

  8. Integral Monotopic Membrane Proteins • Schematicrepresentationofthe different typesofinteractionbetweenmonotopicmembraneproteinsandthecellmembrane: • interactionby an amphipathicα-helix parallel tothemembrane plane (in-plane membranehelix) • interactionby a hydrophobicloop • interactionby a covalentlyboundmembranelipid (lipidation) • electrostaticorionicinteractionswithmembranelipids (e.g.through a calciumion)

  9. The First 3D Membrane Protein Structure

  10. Membrane Protein Databases http://blanco.biomol.uci.edu/mpstruc/listAll/list

  11. Membrane Protein Databases www.mpdb.tcd.ie

  12. Membrane Protein Databases opm.phar.umich.edu

  13. Membrane Protein Databases opm.phar.umich.edu

  14. Membrane Protein StructureClasses

  15. Protein Orientation in Membranes

  16. Transmembrane Protein (Halorhodopsin) alpha-helical polytopic

  17. Transmembrane Protein (Halorhodopsin) alpha-helical 1e12

  18. Transmembrane Protein (Halorhodopsin) alpha-helical 1e12

  19. Transmembrane Protein (Outer Membrane Protein A) beta-barrel

  20. Transmembrane Protein (Outer Membrane Protein A) beta-barrel 1qjp

  21. Monotopic Membrane Protein

  22. 1bhp

  23. Transmembrane Helix Prediction Server www.cbs.dtu.dk/services/TMHMM/

  24. FASTA Format >sp|P16102|BACH_HALSA Halorhodopsin OS=Halobacterium salinarium (strain ATCC 700922) MSITSVPGVVDAGVLGAQSAAAVRENALLSSSLWVNVALAGIAILVFVYMGRTIRPGRPR LIWGATLMIPLVSISSYLGLLSGLTVGMIEMPAGHALAGEMVRSQWGRYLTWALSTPMIL LALGLLADVDLGSLFTVIAADIGMCVTGLAAAMTTSALLFRWAFYAISCAFFVVVLSALV TDWAASASSAGTAEIFDTLRVLTVVLWLGYPIVWAVGVEGLALVQSVGVTSWAYSVLDVF AKYVFAFILLRWVANNERTVAVAGQTLGTMSSDD

  25. Transmembrane Helix Prediction Server (1e12) www.cbs.dtu.dk/services/TMHMM/

  26. Transmembrane Helix Prediction Server (1e12) www.cbs.dtu.dk/services/TMHMM/

  27. Split Server split.pmfst.hr/split/4/

  28. Split Server Prediction (1e12) split.pmfst.hr/split/4/

  29. Split Server Prediction (1qjp) split.pmfst.hr/split/4/

  30. Other Tools for Membrane Protein StructurePrediction http://www.stats.ox.ac.uk/~kelm/medeller/

  31. iMembranePrediction (1e12)

  32. iMembranePrediction (1e12)

  33. Transmembrane Prediction Sites http://expasy.org/tools/ http://www.sacs.ucsf.edu/Links/transmem.html

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