The lateral side of the TLR5 receptor forms and extensive primary binding interface with the 3 α- helices of the D1 domain of FliC. This large interface can be separated into two spatially separate sections, interface A and interface B.
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| Figure 3.1 Overview of the primary interface. Residues involved in interface A are coloured blue (FliC) and light blue (TLR5). Interface B is coloured red (FliC) and pink (TLR5). |
The primary interface is responsible for the recognition and binding of the FliC protein, forming the 1:1 heterodimer. The FliC residues involved in the interface are believed to also be involved in the oligomerization of the flagellar filament, making them highly conserved across different species and strains.
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| Figure 3.2 Interactions of interface A |
The main hydrophilic interactions of interface A are formed between the terminal end of the αCD1 helix of FliC (coloured magenta) and the concave and lateral sides of TLR5 (coloured green). The residues between the two proteins form 5 H-bonds and 3 salt bridges. The Leucine Rich Repeats (LRR) of TLR5, LRRNT-LRR6, each contribute a few residues towards the binding interface. Interface A grows narrower as it ascends as LRR3-LRR6 contribute fewer residues than LRRNT-LRR2.
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| Figure 3.3 Interactions of interface B |
Interface B comprises of hydrophilic interactions between the LRR in the center of the TLR5 protein (LRR7-LRR10) and the upper sections of the two N-terminal α-helices of FliC (αND1a and αND1b). This interface forms 60% of the buried surface accessible area and contains 12 H-bonds making it form the majority of the primary interface. Binding primarily occurs at the LRR9 loop (coloured dark blue) protruding from the convex surface. This loop is initially flexible but forms a well-defined groove upon FliC binding. This groove is key for FliC binding as it is responsible for 50% of the H-bonds found in the primary interface.
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| Figure 3.4 Key interactions between conserved FliC residues and the TLR5 hydrophilic groove |
Arg 90 and Glu 114 are 2 absolutely conserved residues of FliC that interact with the groove formed by the LRR9 loop. Arg 90 forms 4 hydrogen bonds with TLR5 Tyr 267, Gly 270, and Ser 271. FliC Glu 114 orientates the Arg 90 side chain into the TLR5 groove, as well as forming a H- bond to Asn 277.
Making the cartoon version of the entire protein partially transparent is really effective- especially when the stick forms are clear as it puts these residues into context!
ReplyDeleteI don't know why, but for some reason there's a flash in the last GIF on this page!
Generally good GIFs. It would be better if the labels and the interactions in Figure 3.3 is deleted and shown in a separate figure. it looks a little bit messy in that figure.
ReplyDeleteBy far the highest number of GIFs that I have seen in a blog yet! very helpful in helping us picture how the protein looks like in 3D space. The labels that rotate with the GIFs are especially helpful, but in some GIFs the labels are far too numerous and small to read. For those cases perhaps it would be better if you show the region of interest as a zoomed-in image instead? very nice blog!
ReplyDeleteGIFs are very powerful tools to illustrate your points, especially protein structures like this. But I agree that there are too many labels in some of them, perhaps you can label residues that have significant functions only? Otherwise, your blog is well-structured and fun to read!
ReplyDelete