Reader Comments

Re: Generic versus Non-Generic Interfaces

by Douglas Axe (2010-08-23)

In response to Generic versus Non-Generic Interfaces

Thank you for your comments, Jiří.

You've asked first whether my discussion of the non-generic nature of binding interfaces, particularly the interfaces between protein domains, implies that there should be no backbone connections between domains (if I've understood you correctly).

No, I didn't mean to imply that. As you can see in Figure 9 of the paper, there are in this case two backbone connections between the two domains. When we speak of the binding interface between protein domains we're typically referring to the non-covalent interactions (as with protein-protein binding). You're right that there are backbone connections in the case of multi-domain proteins, but these typically account for only a small fraction of the whole interface.

And in the experiment described with Figure 9, those covalent backbone connections are preserved. The problem is that the non-covalent interactions, being highly sequence dependent, are badly messed up when domains are interchanged in this way.

Your second question is, I think, answered in the paper: "the only possible generic additions at these interfaces are those that extend the regular structure, either by elongating the helix or by adding a strand to the edge of the sheet. Although examples of proteins accommodating these structural changes certainly exist [47, 48], the fact that both simply extend existing structure makes them unhelpful for explaining wholesale structural reorganization."

In other words, while these generic extension are possible in many cases, they are modest in scale, and they don't give you a new fold.


ISSN: 2151-7444