Gaucher Disease: Task 03 - Sequence-based predictions

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Revision as of 16:52, 27 May 2013 by Gerkej (talk | contribs) (Transmembrane Helices)

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
Cartoon P04062.png
Graphik P04062.png
1ogs.png
-
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
Cartoon Q9YDF8.png
Graphik Q9YDF8.png
1ors-Q9YDF.png
1ors lm.png
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
Cartoon P47863.png
Graphik P47863.png
2d57.png
2d57 lm.png
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
Cartoon P35462.png
Graphik P35462.png
3pbl.png
3pbl lm.png
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/

Which predictions can be improved considerably by structure-based approaches