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- 2013/2014 - 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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slide1

- 2013/2014 -

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/

slide5

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.

slide6

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 …]

slide7

Integral Polytopic Membrane (Transmembrane) Proteins

  • Schematicrepresentationoftransmembraneproteins:
  • a singletransmembraneα-helix (bitopicmembraneprotein)
  • a polytopictransmembraneα-helicalprotein
  • a polytopictransmembraneβ-sheetprotein
slide8

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)
slide10

Membrane Protein Databases

http://blanco.biomol.uci.edu/mpstruc/listAll/list

slide11

Membrane Protein Databases

http://blanco.biomol.uci.edu/mpstruc/listAll/list

slide13

Membrane Protein Databases

opm.phar.umich.edu

slide14

Membrane Protein StructureClasses

January 2013

January 2014

slide23

Transmembrane Helix Prediction Server

www.cbs.dtu.dk/services/TMHMM/

slide24

FASTA Format

>sp|P16102|BACH_HALSA Halorhodopsin OS=Halobacterium salinarium (strain ATCC 700922)

MSITSVPGVVDAGVLGAQSAAAVRENALLSSSLWVNVALAGIAILVFVYMGRTIRPGRPR

LIWGATLMIPLVSISSYLGLLSGLTVGMIEMPAGHALAGEMVRSQWGRYLTWALSTPMIL

LALGLLADVDLGSLFTVIAADIGMCVTGLAAAMTTSALLFRWAFYAISCAFFVVVLSALV

TDWAASASSAGTAEIFDTLRVLTVVLWLGYPIVWAVGVEGLALVQSVGVTSWAYSVLDVF

AKYVFAFILLRWVANNERTVAVAGQTLGTMSSDD

slide25

Transmembrane Helix Prediction Server (1e12)

www.cbs.dtu.dk/services/TMHMM/

slide26

Transmembrane Helix Prediction Server (1e12)

www.cbs.dtu.dk/services/TMHMM/

slide27

Split Server

split.pmfst.hr/split/4/

slide28

Split Server Prediction (1e12)

split.pmfst.hr/split/4/

slide29

Split Server Prediction (1qjp)

split.pmfst.hr/split/4/

slide30

Other Tools for Membrane Protein StructurePrediction

http://www.stats.ox.ac.uk/~kelm/medeller/

slide33

Transmembrane Prediction Sites

http://expasy.org/tools/

slide34

Transmembrane Prediction Sites

http://www.sacs.ucsf.edu/Links/transmem.html