P53R2: Difference between revisions
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M2 and p53R2 interact with M1 through the C-terminal binding domain. These two subunits share more than 80% sequence identity. But the few differences between the two are not unimportant, as it’s explained below. | M2 and p53R2 interact with M1 through the C-terminal binding domain. These two subunits share more than 80% sequence identity. But the few differences between the two are not unimportant, as it’s explained below. | ||
The first X-ray crystal structure of p53R2 has a resolution of 2,6 Å and permits to describe its structure and also to show the structural differences with the M2 subunit. | The first X-ray crystal structure of p53R2 has a resolution of 2,6 Å and permits to describe its structure and also to show the structural differences with the M2 subunit (Figure 1). | ||
=='''Structure and function'''== | =='''Structure and function'''== | ||
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<scene name='Sandbox156/Iron-binding_site/2'>An iron-binding site</scene> is highlighted. But concerning this site, the two monomers are not the same. Actually, the B monomer has two iron-binding site (called Fe2 and Fe1) whereas the A monomer has only one which is Fe2. This can be explained by structural changes in the helix that compose the two monomers. The 37 to 42 N-terminal residues (called the swivel loop) from one monomer can rotate between two conformations and can influence the position of the helix B or D on the opposite monomer. | <scene name='Sandbox156/Iron-binding_site/2'>An iron-binding site</scene> is highlighted. But concerning this site, the two monomers are not the same. Actually, the B monomer has two iron-binding site (called Fe2 and Fe1) whereas the A monomer has only one which is Fe2. This can be explained by structural changes in the helix that compose the two monomers. The 37 to 42 N-terminal residues (called the swivel loop) from one monomer can rotate between two conformations and can influence the position of the helix B or D on the opposite monomer. | ||
[[Image:Thetwomonomers.jpg|400px]] | [[Image:Thetwomonomers.jpg| Figure 1: The structure of the p53R2 protein is shown. P53R2 is built up by two monomers A and B, which contain several iron-binding sites. | 400px]] | ||
The N-terminal residues of the monomer A can stabilize the B helix of the monomer B due to different interactions. R41 of the monomer A forms a salt bridge with E119 of monomer A. This interaction permits the formation of a H-bond between R40 of monomer A with G101of monomer B. Furthermore K37 in monomer A forms a salt bridge with E105 of monomer B and this stabilize its B helix. All the interactions allow D100 of monomer B to be well oriented to bind Fe1 (see Figure | The N-terminal residues of the monomer A can stabilize the B helix of the monomer B due to different interactions. R41 of the monomer A forms a salt bridge with E119 of monomer A. This interaction permits the formation of a H-bond between R40 of monomer A with G101of monomer B. Furthermore K37 in monomer A forms a salt bridge with E105 of monomer B and this stabilize its B helix. All the interactions allow D100 of monomer B to be well oriented to bind Fe1 (see Figure 2, Smith P. et al., <ref>PMID:19728742</ref>). | ||
[[Image:Figure 1.jpg | thumb | Shown are the interactions between the N-terminal loop of monomer A and the continuous helix B of monomer B with the iron binding sites Fe1 and Fe2. | center]] | [[Image:Figure 1.jpg | thumb | Figure 2: Shown are the interactions between the N-terminal loop of monomer A and the continuous helix B of monomer B with the iron binding sites Fe1 and Fe2. | center]] | ||
On the contrary R40 of monomer B is bound to E119 of the same monomer and so it can not bind to G101 of the monomer A and the consequence is that F42 disturb the B helix of monomer A. D100 can not interact with Fe1. This explain why the monomer A has only one iron-binding site whereas the monomer B has two (see Figure | On the contrary R40 of monomer B is bound to E119 of the same monomer and so it can not bind to G101 of the monomer A and the consequence is that F42 disturb the B helix of monomer A. D100 can not interact with Fe1. This explain why the monomer A has only one iron-binding site whereas the monomer B has two (see Figure 3, Smith P. et al. <ref>PMID:19728742</ref>). | ||
[[Image:Figure 2.jpg | thumb | Shown are the interactions between the N-terminal loop of monomer B and the discontinuous helix B of monomer A with the iron binding site Fe2. | center]] | [[Image:Figure 2.jpg | thumb | Figure 3: Shown are the interactions between the N-terminal loop of monomer B and the discontinuous helix B of monomer A with the iron binding site Fe2. | center]] | ||
Compare to the M2 subunit, these iron-binding sites are less efficient. This is due to the different conformations that the p53R2 subunit can adopt (stabilization or not of the two helix B and D). | Compare to the M2 subunit, these iron-binding sites are less efficient. This is due to the different conformations that the p53R2 subunit can adopt (stabilization or not of the two helix B and D). | ||