How to interprete the tertiary structure? - (Sep/18/2006 )
Hi all,
I use SWISS-MODEL to predict the tertiary strcuture of neurotrophic tyrosine kinase receptor and use Rasmol to open it. I am trying to make sense out of this tertiary structure.
Can i say there are 7 beta strands, which may represent the transmembrane region of the receptor? How should i interprete the result?
hmm interesting.
from that image it looks like there are only six sheets - maybe one short section on the right hand side pressing up against the other sheets. You used Swiss-Model to make this - how good was the alignment etc - are there several models there - I can see what looks like 4 termini.
If you alignment is shoddy your models will be too.... could you post the pdb file containing the coordinates. I don't know how much data is available on neurotrophic kinase receptors so i ask this - is cimparative modelling suitable for this work?
what about it forming a dimer or trimer etc - you can't assign/speculate about a function based on this structure - unless you have a similar structure with high sequence identity with known function...
from that image it looks like there are only six sheets - maybe one short section on the right hand side pressing up against the other sheets. You used Swiss-Model to make this - how good was the alignment etc - are there several models there - I can see what looks like 4 termini.
If you alignment is shoddy your models will be too.... could you post the pdb file containing the coordinates. I don't know how much data is available on neurotrophic kinase receptors so i ask this - is cimparative modelling suitable for this work?
what about it forming a dimer or trimer etc - you can't assign/speculate about a function based on this structure - unless you have a similar structure with high sequence identity with known function...
Comparative modelling is suitable. Actually, it is an assignment and i am supposed to make some "stories" that make sense about this protein.
I did BLASTp and found that it is homologous to skeletal muscle receptor of mice (NP_035074.2), which plays a role in the organization of the postsynaptic membrane and synaptic gene transcription. Two sequence alignment using Lalign shows more than 50% identity and very good score and E-value. So, i say neurotrophic kinase receptors may involve is message delivery across the synapse.
Then i predict the 3D strucure using SWISS-MODEL and get this strucure, and i am lost here. I dunno how to inteprete the result...
?trying to upload the pdb file but failed.
"Upload failed. You are not permitted to upload a file with that file extension."
"I did BLASTp and found that it is homologous to skeletal muscle receptor of mice (NP_035074.2), which plays a role..."
is there a structure for skeletal muscle receptor? Are there structures for any of the things that you aligned your seed with?
is there a structure for skeletal muscle receptor? Are there structures for any of the things that you aligned your seed with?
not really, i did a search in Brookhaven Protein Databank (PDB) but the results do not look good.
I am trying to prove that the seven helixes are the transmembrane region. What i did was,i aligned rhodopsin (a G-protein coupled receptor with 7 helical transmembrane regions) with my seed (NTRK1) using ClustalW and the result shows a lot of "*" and ":" (i assume this means good alignment)
can i use this to support my assumption?
Hey,
there is a big difference between alignment of sequence and alignment of structure. For a successful comparative model you need 1) a structure 2) the sequence of that structure. What you want is for your sequence (the target from now on) to have high sequence identity with a sequence with KNOWN structure (template). Armed with the alignment of the target sequence to the template sequence-structure you can use Swiss-model to build a comparative model. The grewat thing about a comparative model is that because the target and template are so similar you (the program) only needs to account for mild changes (Leu -> Val) - basically the overall topology of the backbone is good leaving you to only make changes to side chain angles.
As the sequence similarity between the target and template drops the quality (and amount of potential error) increases - see papers involving the twilight zone and threading. If you have not been able to identify a structure with decent sequence similarity to your target then maybe you shouldn't be looking at a swiss model structure - or you should be very sure to make you doubts about its quality known.
As far as sequence sequence comparisos go (i.e. no regard for protein structure) you can attempt to infer some functional details - you could try, as you have done, to search for sequences with known function and imply that they is common function - you could also supplement this by search databases such as prints or prodom to find small function motifs in your sequence.
I assume your first step was to use psi-blast and the NR database to identify similar sequences.... I would also avoid the use of clustal, instead opting for MUSCLE to complete clustering.
I hope this makes some sense - I have only had one cup of weak coffee today... I must have more!!!! 