Gaucher Disease: Task 03 - Sequence-based predictions
Contents
Secondary Structure
In this task secondary structure is predicted using ReProf and PsiPred and compared to DSSP structure assignment. ReProf uses a fasta sequence or a PSI-BLAST PSSM for prediction, PsiPred a fasta sequence and DSSP server needs a PDB file in order to use the 3D coordinates of atoms. The predictions were made for the proteins below. If several PDB structures are available, the one covering the longest sequence and with the best resolution was chosen. For glucosylceramidase the structure 1OGS was used (as in the previous week task).
Uniprot | PDB | |||||||
---|---|---|---|---|---|---|---|---|
Entry | Protein name | Origin | Length | Entry | Method | Resolution (Å) | Chain | Positions |
P10775 | Ribonuclease inhibitor | pig | 456 AA | 2BNH | X-ray | 2.30 | A | 1-456 |
Q9X0E6 | Divalent-cation tolerance protein CutA | bacterium Thermotoga maritima | 101 AA | 1KR4 | X-ray | 1.40 | A | 1-101 |
Q08209 | Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, EC=3.1.3.16 | human | 521 AA | 1AUI | X-ray | 2.10 | A | 1-521 |
P04062 | Glucosylceramidase/acid-beta-glucosidase, EC=3.2.1.45 | human | 536 AA | 1OGS | X-ray | 2.00 | A/B | 40-536 |
TODO: What features are predicted? Discuss the results for your protein and the example proteins. Using the predictions, what could you learn about your protein and the example proteins? Compare to the available knowledge in UniProt, PDB, DisProt, OPM, PDBTM, Pfam...
Disorder
Transmembrane Helices
Four Proteins, including the Gaucher's disease causing Protein, where analysed under reference by transmembrane helices. The used prediction tools differ in their analysing features. While Polyphobius only differs between residues being part of a transmembrane helix or being inside/outside of the cytoplama, Memsat-SVM also predicts re-entrant helices and pore-linig helices. Due to the fact that pore-lining helices are also transmembrane helices, this kind of helices is detected of both prediction tools. In case of re-entrant helices both programms differ. In general a membrane helix crosses the membrane, so that both ends of the helix lie on different sides of the membrane. In contrast, the re-entrant helix leads bot its ends to the same side of the mebrane. Memsat-SVM can predict re-entrant helices, but Polyphobius treats this helices as a general membrane helices, which crosses the membrane (seen for Q9YDF8), or ignores it (seen for). In case of re-entrant helices predictions also the C-terminal or the N-terminal may be predicted on different membrane sides, as well as some helices may be predicted to lie in a different direction within the membrane, because of an re-entrant helix.
Comparison of TMH for P04062 | ||||
---|---|---|---|---|
Prediction | Assignment | |||
Memsat SVM | Polyphobius | OPM | PDMTM | |
# of TMH | 1 | - | - | - |
TMH Topology | 456-471 | - | - | - |
N-terminal | extracellular | extracellular | extracellular | - |
C-terminal | cytoplasmic | extracellular | extracellular | - |
Signal peptide | 1-34 | 1-40 | - | - |
Re-entrant Helix | - | - | - | - |
Pore-lining Helix | 1 | - | - | - |
Graphical position | - | |||
more information | P04062 | 1OGS | 1OGS is not in the PDBTM |
Comparison of TMH for Q9YDF8 | ||||
---|---|---|---|---|
Prediction | Assignment | |||
Memsat SVM | Polyphobius | OPM | PDMTM | |
# of TMH | 6 | 7 | 5 | 4 |
TMH Topology | 43-59 72-90 101-118 128-143 163-184 221-245 |
42-60 68-88 108-129 137-157 163-184 196-213 224-244 |
25-46 55-78 86-97 100-107 117-148 |
27-50 55-75 88-107 118-142 |
N-terminal | cytoplasmic | extracellular | cytoplasmic | cytoplasmic |
C-terminal | cytoplasmic | cytoplasmic | cytoplasmic | cytoplasmic |
Signal peptide | - | - | ||
Re-entrant Helix | 188-217 | - | ||
Pore-lining Helix | 1 | - | ||
Graphical position | ||||
more information | Q9YDF8 | 1ORS | 1ORS |
Comparison of TMH for P47863 | ||||
---|---|---|---|---|
Prediction | Assignment | |||
Memsat SVM | Polyphobius | OPM | PDMTM | |
# of TMH | 6 | 6 | 8 (per chain) | 8 (per chain) |
TMH Topology | 35-56 71-89 113-136 157-178 190-205 232-252 |
34-58 70-91 115-136 156-177 188-208 231-252 |
34-56 70-88 98-107 112-136 156-178 189-203 214-223 231-252 |
39-55 72-89 95-106 116-133 158-177 188-205 209-222 231-248 |
N-terminal | extracellular | cytoplasmic | cytoplasmic | cytoplasmic |
C-terminal | extracellular | cytoplasmic | cytoplasmic | cytoplasmic |
Signal peptide | 1-20 | |||
Re-entrant Helix | 93-109 209-225 |
95-106 209-222 | ||
Pore-lining Helix | 4 | |||
Graphical position | ||||
more information | P47863 | 2D57 | 2D57 |
Comparison of TMH for P35462 | ||||
---|---|---|---|---|
Prediction | Assignment | |||
Memsat SVM | Polyphobius | OPM | PDMTM | |
# of TMH | 6 | 7 | 7 | 7 |
TMH Topology | 32-55 65-88 101-129 151-169 188-209 331-354 |
30-55 66-88 105-126 150-170 188-212 329-352 367-386 |
34-52 67-91 101-126 150-170 187-209 330-351 363-386 |
35-52 68-84 109-123 152-166 191-206 334-347 368-382 |
N-terminal | extracellular | extracellular | extracellular | extracellular |
C-terminal | extracellular | cytoplasmic | cytoplasmic | cytoplasmic |
Signal peptide | 1-29 | - | ||
Re-entrant Helix | - | - | - | |
Pore-lining Helix | 1 | |||
Graphical position | ||||
more information | P35462 | 3PBL | 3PBL |
Signal Peptides
GO Terms
Discussion
Other available methods
Prediction of | Tool | Information |
---|---|---|
secondary structure | GOR | http://gor.bb.iastate.edu/ |
disorder | DISOPRED2 | http://bioinf.cs.ucl.ac.uk/psipred/ |
transmembrane helices | MEMSAT3 | http://bioinf.cs.ucl.ac.uk/psipred/ |
TMHMM | http://www.cbs.dtu.dk/services/TMHMM/ | |
signal peptides | ||
GO terms |
What else can/is be predicted from protein sequence alone
- Fold recognition (profile based pGenTHREADER and rapid GenTHREADER)
- Fold domain recognition (pDomTHREADER)
- Protein domain prediction (DomPred)
- Homology modelling (BioSerf v2.0)
- Function prediction (eukaryotic function: FFPred v2.0)
- Prediction of TM topology and helix packing (SVM-based MEMPACK)
http://bioinf.cs.ucl.ac.uk/psipred/