User:Peyton Jenkins/Sandbox 1
From Proteopedia
(Difference between revisions)
| Line 12: | Line 12: | ||
[[STK11]] can be broken down into 3 domains. An N-terminal domain (aa 1-42), kinase domain (aa 43-347), and a C-terminal domain (aa 348-433). The <scene name='10/1078094/Active_site/1'>activation loop</scene> of [[STK11]] is located from residues ~202-212. Within the activation loop is F204, which interacts with a hydrophobic pocket on MO25, which is necessary to stabilize the active conformation. Within the αC helix is residue D98 which forms a <scene name='10/1078094/78and98/2'>salt bridge</scene> with K78, further stabilizing the active site and aids in ATP binding. Mg<sup>2+</sup> helps aid ATP binding, however in this structure there is a point mutation (<scene name='10/1078094/D194a/1'>D194A</scene>) to make STK11 catalytically inactive. Another loop, the <scene name='10/1078094/B2b3_loop/2'>β2-β3 loop</scene> is essential for binding of STRADα on the N-terminal lobe of STK11. β7-β8 sheets of STK11 also interact with STRADα. In the β2-β3 loop R74 hydrogen bonds with Q251 of STRADα. | [[STK11]] can be broken down into 3 domains. An N-terminal domain (aa 1-42), kinase domain (aa 43-347), and a C-terminal domain (aa 348-433). The <scene name='10/1078094/Active_site/1'>activation loop</scene> of [[STK11]] is located from residues ~202-212. Within the activation loop is F204, which interacts with a hydrophobic pocket on MO25, which is necessary to stabilize the active conformation. Within the αC helix is residue D98 which forms a <scene name='10/1078094/78and98/2'>salt bridge</scene> with K78, further stabilizing the active site and aids in ATP binding. Mg<sup>2+</sup> helps aid ATP binding, however in this structure there is a point mutation (<scene name='10/1078094/D194a/1'>D194A</scene>) to make STK11 catalytically inactive. Another loop, the <scene name='10/1078094/B2b3_loop/2'>β2-β3 loop</scene> is essential for binding of STRADα on the N-terminal lobe of STK11. β7-β8 sheets of STK11 also interact with STRADα. In the β2-β3 loop R74 hydrogen bonds with Q251 of STRADα. | ||
=== STRADα === | === STRADα === | ||
| - | STRAD alpha is composed of 2 domains, an N-terminal domain (aa 1-58) and [[pseudokinase]] domain (aa 59-347). STRADα is termed a [[pseudokinase]] because it shares structural features, such as | + | STRAD alpha is composed of 2 domains, an N-terminal domain (aa 1-58) and [[pseudokinase]] domain (aa 59-347). STRADα is termed a [[pseudokinase]] because it shares structural features, such as an activation loop and αC helix, with other kinases, but lacks catalytic activity. STRADα binds STK11 through its pseudokinase domain, with the activation loop interacting with the the β2-β3 loop and β7-β8 sheets of STK11. The αC of STRADα interacts with the surface of MO25, further stabilizing the interaction between proteins. Additionally there is a WEF motif (aa 429-431) on the C-terminus of STRADα interacting with the C-terminus of MO25. |
=== MO25 === | === MO25 === | ||
MO25 is a repeat of α-helices spanning the entire length of the protein. Residues R240 and F243 interact with the A205 and A206 of the STK11 activation loop. This is not required for MO25 and STK11 binding, however mutating R240 and F243 resulted in a catalytically inactive complex, thus these residues are essential to orient and stabilize the active conformation of STK11. | MO25 is a repeat of α-helices spanning the entire length of the protein. Residues R240 and F243 interact with the A205 and A206 of the STK11 activation loop. This is not required for MO25 and STK11 binding, however mutating R240 and F243 resulted in a catalytically inactive complex, thus these residues are essential to orient and stabilize the active conformation of STK11. | ||
Revision as of 14:59, 30 April 2025
2WTK: Hetertrimeric Complex of STK11, MO25, and STRADα
| |||||||||||
