Molecular Playground/DnaK: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Joseph Tilitsky, Michal Harel

@@ Line 15: / Line 15: @@
 ===Function===
-DnaK binds stretches (7-8 residues in length) of exposed hydrophobic residues of its client proteins, in the beta-basket of the SBD, in order to prevent their aggregation.[http://www.ncbi.nlm.nih.gov/pubmed/14740253] Upon ATP binding, the NBD subdomains rotate relative to each other and induce a conformational change in the NBD (compare the <scene name='60/609794/Subdomain_iib/1'>ADP-bound</scene> NBD to the <scene name='60/609794/Nbd-atp/2'>ATP-bound</scene> form  [http://proteopedia.org/wiki/index.php/Image:Superimposed_nbd.png#filelinks|300px|right|thumb| here] (the ATP-bound NBD is shown in lighter colors).[http://www.ncbi.nlm.nih.gov/pubmed/21482798] When ATP binds the NBD, the interdomain linker communicates the allosteric signal to the SBD that induces a conformational change in the SBD, causing the alpha-helical lid to dock onto the NBD. Compare the <scene name='60/609794/Sbd_open/2'>open</scene> form of the SBD (when the NBD binds ATP) and the <scene name='60/609794/Helical_lid/1'>closed</scene> form of the SBD (when the NBD binds ADP) [http://proteopedia.org/wiki/index.php/Image:Superimposed_sbd.png#filelinks|300px|right|thumb| here].
+DnaK binds stretches (7-8 residues in length) of exposed hydrophobic residues of its client proteins, in the beta-basket of the SBD, in order to prevent their aggregation.[http://www.ncbi.nlm.nih.gov/pubmed/14740253] Upon ATP binding, the NBD subdomains rotate relative to each other and induce a conformational change in the NBD (compare the <scene name='60/609794/Subdomain_iib/1'>ADP-bound</scene> NBD to the <scene name='60/609794/Nbd-atp/2'>ATP-bound</scene> form  [http://proteopedia.org/wiki/index.php/Image:Superimposed_nbd.png#filelinks|300px|right|thumb| here] (the ATP-bound NBD is shown in lighter colors).[http://www.ncbi.nlm.nih.gov/pubmed/21482798] When ATP binds the NBD, the interdomain linker communicates the allosteric signal to the SBD that induces a conformational change in the SBD, causing the alpha-helical lid to dock onto the NBD. Compare the <scene name='60/609794/Sbd_open/2'>open</scene> form of the SBD (when the NBD binds ATP) and the <scene name='60/609794/Helical_lid/1'>closed</scene> form of the SBD (when the NBD binds ADP). [http://proteopedia.org/wiki/index.php/Image:Superimposed_sbd.png#filelinks|300px|right|thumb| here]
 [http://www.ncbi.nlm.nih.gov/pubmed/17434124?dopt=Abstract] The alpha-helical lid of the SBD rotates 180 degrees during the closing motion.[http://www.ncbi.nlm.nih.gov/pubmed/23123194?dopt=Abstract] The result is that the same residues that dock with the NBD are responsible for binding the nascent chain of the client. The SBD has low substrate affinity in the 'open' conformation, but high substrate affinity in the 'closed' conformation.[http://www.ncbi.nlm.nih.gov/pubmed/24012426] Upon ATP hydrolysis, the NBD reverts to the ADP-bound state, undocking the alpha-helical lid from the NBD and regenerating the 'closed' conformation of the SBD. Alternating cycles of binding and release allow DnaK to unfold kinetically trapped intermediates and allow the client protein to refold to its native state.[http://www.ncbi.nlm.nih.gov/pubmed/20953191] Recently, a third 'allosterically active' state of DnaK has been discovered. In this state, the two domains remain undocked, with the SBD retaining high substrate affinity, but the interdomain linker is bound to the NBD. This state occurs when both ATP and substrate are bound simultaneously and has not yet been crystallized.[http://www.ncbi.nlm.nih.gov/pubmed/23217711]