Identifying proteins by structure

[John37309]

Identifying proteins by structure

Can proteins be identified by their structural image alone?

What do i mean by that? Well i understand the basics of protein folding and protein structure. I have a basic understanding of primary, secondary and tertiary structure of DNA/RNA. But i want to understand these images better.

Lets take Myoglobin as an example; http://en.wikipedia.org/wiki/Myoglobin

Quote Wikipedia;
" It has eight alpha helices and a hydrophobic core."

So can Myoglobin be identified by that picture alone? If i look at the picture, i can see 4 very large alpha helices and 4 smaller alpha helices. These are joined by short RNA strings.

In that Myoglobin image for example, the red alpha helices has 6 turns in the helix. Obviously if the red alpha helices had 10 turns instead of 6 turns, it would not be a Myoglobin protein. But my question is can proteins be identified just by counting the number of alpha helices and the number of turns in those individual alpha helices?

Is there any simple rule-of-thumb that you can use to allow you to identify different proteins just from the images?

John.

 

[Ryan_m_b]

Do you mean in principle or can normal people do it? X-ray crystallography only determines proteins by their structure and compares them to a database (IIRC, it's been a while). As for if one can simply look at a picture and know the answer is yes, but obviously it depends on your experience. Some proteins look very similar and it's easy to get it wrong but when you are working with/studying one protein you tend to be able to pick it out. Of course if you ever needed to examine a protein properly you wouldn't do it by eye and if you were looking at a picture in an article or book it would have the name.

 

[mishrashubham]

I have a basic understanding of primary, secondary and tertiary structure of DNA/RNA. But i want to understand these images better.

Lets take Myoglobin as an example; http://en.wikipedia.org/wiki/Myoglobin

Quote Wikipedia;
" It has eight alpha helices and a hydrophobic core."

So can Myoglobin be identified by that picture alone?...

In that Myoglobin image for example, the red alpha helices has 6 turns in the helix. Obviously if the red alpha helices had 10 turns instead of 6 turns, it would not be a Myoglobin protein. But my question is can proteins be identified just by counting the number of alpha helices and the number of turns in those individual alpha helices?

Is there any simple rule-of-thumb that you can use to allow you to identify different proteins just from the images?

Alpha helices are not the only thing proteins are made of. The basic secondary structural elements of alpha helices and beta sheets, form more complex secondary structures called motifs. And many such motifs pack together to make proteins domains which make tertiary structure of proteins.
The domains are separate units which evolve independently and can be reshuffled to form entirely new proteins. And it is these domains which give characteristic shapes to proteins and each one can have its own active site having functions which can be quite from other domains in rest of the protein.
Myoglobin is a small single domain protein but most proteins are multi domain structures. Yes classes of proteins can be identified by certain characteristic motifs but pinpointing a specific one is not the purpose of ribbon diagrams. They only help to visualize the protein and understand correlation between structural and functional elements.

These are joined by short RNA strings.

I think you meant amino acids.

 

[John37309]

Thanks guys,
See i have been looking at those images of proteins for years, but never really knowing exactly what I'm looking at.

This question is a bit like looking at cars. If you show a picture of a car to a expert, he will tell you exactly what make and model the car is, maybe even its year of manufacture. So the car expert might never have seen a Nissan Micra car, but if you showed him the picture of one, he would recognise the image straight away, even though there are tens of thousands of types of cars in the world. So even though all cars look roughly the same shape, they all have similar structure, its common for people to identify them from an image alone, and no other information.

So applying that to DNA, proteins, genes and other biological structural images, can a trained expert identify some of these things just by the image alone?

Quote mishrashubham;

"Yes classes of proteins can be identified by certain characteristic motifs but pinpointing a specific one is not the purpose of ribbon diagrams"

So what exactly is the purpose of ribbon diagrams?

mishrashubham could you roughly identify classes of proteins just from those ribbon diagrams? I mean would you know roughly what group a protein might be just by seeing a particular motif inside a ribbon diagram or structural motif? - http://en.wikipedia.org/wiki/Structural_motif

John.

 

[Mike H]

You may be interested in the following websites -

http://scop.mrc-lmb.cam.ac.uk/scop/

and

http://www.cathdb.info/

While someone can recognize it quite well in just a ribbon representation - it's not hard to recognize a TIM barrel, or coiled-coil, or SH3 domain (or your favorite motif) that's flashed up on a screen if you know what they are - without additional detail, that's about all you can definitively say. These sorts of folds/motifs are fairly ubiquitous.

A ribbon representation is one that is generally intended to present the overall fold of the protein. They are not an optimal choice if you want to show the details of a catalytic active site, for instance, or if you want to elaborate upon a ligand-binding site.

 

[John37309]

Mike,
Thanks for the links. Yes, i think that's exactly what i need! I have been reading general info about individual proteins on Wikipedia without first knowing the basics of what I'm looking at in the images. Those websites might give me a short crash coarse in how to identify the basic structural motif's. I think that's what i need, i need to learn the basic structures first!

Good sites, looks like i have some reading to do :)

Thanks Mike!
John.

 

[mishrashubham]

Another site you may like.
http://www.ruppweb.org/Xray/tutorial/protein_structure.htm

 

[John37309]

mishrashubham,
Thanks, that looks like a good tutorial. I will take the time to read through it!

So the general impression i get here is that it is possible to some extent to identify some types of proteins just from particular patterns or motifs within the image. But it might not tell you everything about that protein.

Ok, i have lots of reading to do.
John.

 

[Mike H]

Hi John,

It sounds as if you'd be better served by either finding a good biochemistry text or one on protein structure (for example, the one by Branden & Tooze) so you can get a coherent and fairly well-balanced picture of protein structure & function, rather than trying to do things piecemeal.

I think it's important to remember that - as noted earlier - ribbon representations are really only optimal for understanding the overall fold and architecture of a protein or complex thereof. Given that - to take my earlier mention of TIM barrels - the same protein fold is used by multiple classes of proteins (I believe that out of the six standard enzyme classification categories, TIM barrels are found in five of those six categories), being able to recognize a TIM barrel is hardly sufficient to say, "well, that's this aldolase from humans but this other one is an oxidoreductase from yeast." The same applies to protein domains, of course - for example, the PDZ domain is found in everything from bacteria to humans, and as a component in multiple proteins. I used to work with proteins that had PDZ domains - while I can recognize the fold, there's no way I could absolutely determine if a random structure of one was from a human or bacteria based on just a ribbon diagram, or from what protein in humans it was taken from.

 

[John37309]

Mike,
Thank you. I have payed close attention to the advice you have given me. I envy the knowledge you have in this area of science. LOL... I need your head on my shoulders :)

I'm just getting started with this stuff. But i suspect i have many years of work ahead of me. I have a thousand questions to ask, i don't know where to start. So its best if i start from the beginning and learn the basics first.

I won't burden you anymore until i have learned the basics first.
Thank you for the help,
John.

 

[Mike H]

John,

I knew I was forgetting something in my last post. You might find the NIH Bookshelf to be of use here -

http://www.ncbi.nlm.nih.gov/books/

- and in particular the updated Stryer Biochemistry text -

http://www.ncbi.nlm.nih.gov/books/NBK21154/

Of course, if you have questions while in the course of reading and studying, by all means please ask! It's why we're here.

 

[John37309]

Thanks for the help Mike.

John.