Transcript Folie 1 - FLI
- 2011 -
3D Structures of Biological Macromolecules
Exercise: Membrane Proteins
Jürgen Sühnel
Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena Centre for Bioinformatics Jena / Germany
Supplementary Material: http://www.fli-leibniz.de/www_bioc/3D/
Cell Membrane
Membrane Structural Components
Lipids
Cholesterol, a Constituent of the Cell 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.
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 …]
Integral Polytopic Membrane (Transmembrane) Proteins
Schematic representation of transmembrane proteins: 1. a single transmembrane α-helix (bitopic membrane protein) 2. a polytopic transmembrane 3. a polytopic transmembrane α-helical protein β-sheet protein
Integral Monotopic Membrane Proteins
Schematic representation of the different types of interaction between monotopic membrane proteins and the cell membrane: 1. interaction by an amphipathic α-helix parallel to the membrane plane (in-plane membrane helix) 2. interaction by a hydrophobic loop 3. interaction by a covalently bound membrane lipid (
lipidation
) 4. electrostatic or ionic interactions with membrane lipids (
e.g.
through a calcium ion)
The First 3D Membrane Protein Structure
Membrane Protein Databases
http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html
Membrane Protein Databases
www.mpdb.tcd.ie
Membrane Protein Databases
opm.phar.umich.edu
Membrane Protein Databases
opm.phar.umich.edu
Membrane Protein Structure Classes
Membrane Protein Structure Classes
Transmembrane Protein (Halorhodopsin)
alpha-helical
Transmembrane Protein (Halorhodopsin)
alpha-helical 1e12
Transmembrane Protein (Halorhodopsin)
alpha-helical 1e12
Transmembrane Protein (Outer Membrane Protein A)
beta-barrel
Transmembrane Protein (Outer Membrane Protein A)
beta-barrel 1qjp
Monotopic Membrane Protein
1bhp
Transmembrane Helix Prediction Server
www.cbs.dtu.dk/services/TMHMM/
FASTA Format
>sp|P16102|BACH_HALSA Halorhodopsin OS=Halobacterium salinarium (strain ATCC 700922) MSITSVPGVVDAGVLGAQSAAAVRENALLSSSLWVNVALAGIAILVFVYMGRTIRPGRPR LIWGATLMIPLVSISSYLGLLSGLTVGMIEMPAGHALAGEMVRSQWGRYLTWALSTPMIL LALGLLADVDLGSLFTVIAADIGMCVTGLAAAMTTSALLFRWAFYAISCAFFVVVLSALV TDWAASASSAGTAEIFDTLRVLTVVLWLGYPIVWAVGVEGLALVQSVGVTSWAYSVLDVF AKYVFAFILLRWVANNERTVAVAGQTLGTMSSDD
Transmembrane Helix Prediction Server (1e12)
www.cbs.dtu.dk/services/TMHMM/
Transmembrane Helix Prediction Server (1e12)
www.cbs.dtu.dk/services/TMHMM/
Split Server Prediction (1e12)
split.pmfst.hr/split/4/
Other Tools for Membrane Protein Structure Prediction
http://www.stats.ox.ac.uk/~kelm/medeller/
iMembrane Prediction (1e12)
Split Server Prediction (1qjp)
split.pmfst.hr/split/4/
Transmembrane Prediction Sites
http://expasy.org/tools/ http://www.sacs.ucsf.edu/Links/transmem.html