Question: protein 3D model not showing all AA residues
1
gravatar for cocchi.e89
5 weeks ago by
cocchi.e8950
cocchi.e8950 wrote:

Maybe is a silly question but I found no clear information about. I generated the 3D models of a COL4A5 protein with a missense mutation c.2546G>A p.(Gly849Glu) through Phyre2 (here link to my results) and the protein inserted FASTA is ~1690 residues. The generated primary model is only from residue 1464 to 1691. I checked and the model in the COL4A5 UniProt page is identical and relative to this little portion.

My question is: why all the rest of the AA sequence is not showed in the model? If I try to open the relative model from Phyre2 results that is just a long sequence without structure...is there any theoretical reason for that that I am missing? How can I visualize the impact of my mutation on the protein if it does not fall in this little window?

Thank so much in advance

phyre2 mutation protein model • 101 views
ADD COMMENTlink modified 5 weeks ago by Mensur Dlakic4.0k • written 5 weeks ago by cocchi.e8950
1

Phyre specifically only models regions it finds strong homologies for.

If you want full models, I suggest ITASSER, but bear in mind those regions will be of more dubious quality.

ADD REPLYlink written 5 weeks ago by Joe16k

But they have a limitation to 1500 AA sequence. I suppose I cannot cut a portion of the protein and hoping that the results will be reliable, right?

ADD REPLYlink written 5 weeks ago by cocchi.e8950

Yeah the hard limit of 1500 is a bit of a pain. I think, though don't quote me on this, it is possible to edit the source code to remove the limit of 1500, the models just become more and more likely to be spurious. You can indeed split the model and model the domains separately. It's tricky, though not impossible to join them up again later on.

You could try MODELLER or another tool. I'm less familiar with these though so I don't know if they return full length models or just regions like Phyre, or whether they have a large cutoff.

ADD REPLYlink written 5 weeks ago by Joe16k
2
gravatar for Mensur Dlakic
5 weeks ago by
Mensur Dlakic4.0k
USA
Mensur Dlakic4.0k wrote:

The most likely explanation is that there is no homologous structure for the missing part of your model. If you go to the Pfam page for your protein you will see that there are two C4 domains in the part that got modelled. The rest is either of low complexity or collagen, and you may not be able to model it using Phyre2.

ADD COMMENTlink written 5 weeks ago by Mensur Dlakic4.0k

Thanks for the useful answer! Is there any way to model this part?

ADD REPLYlink written 5 weeks ago by cocchi.e8950
1

There is a way to model it, but I don't think there is a way to model it well. See an earlier discussion on a similar topic.

ADD REPLYlink written 5 weeks ago by Mensur Dlakic4.0k
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