Sandbox Reserved 1713: Difference between revisions

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<scene name='90/904318/Phe856/1'>Phe856</scene>
<scene name='90/904318/Phe856/1'>Phe856</scene>
<scene name='90/904318/Arg753/2'>Arg753</scene>
<scene name='90/904318/Arg753/2'>Arg753</scene>
<scene name='90/904318/Gly747/1'>Gly747</scene>
== Relevance ==
== Relevance ==


Revision as of 04:07, 28 March 2022

This Sandbox is Reserved from February 28 through September 1, 2022 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1700 through Sandbox Reserved 1729.
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Anaplastic Lymphoma KinaseAnaplastic Lymphoma Kinase

Anaplastic Lymphoma Kinase is a receptor tyrosine kinase. ALK transfers a phosphate group from ATP to a tyrosine residue on an enzyme which activates a signaling cascade, and ALK becomes activated when a ligand called ALKAL binds to the binding surface on an extracellular domain of ALK. ALK is an integral membrane protein.

Function

Figure 1
Figure 2

Conformational Change

In order for the Anaplastic Lymphoma Kinase (ALK) to move across the membrane to bind with the second monomer, it has to undergo a conformational change. The Anaplastic Lymphoma Kinase Activating Ligand (ALKAL) binds to the binding surface on the ALK. This induces a conformational change which allows for the PXL and the GlyR domains to hinge forward. [1] The kinase is now ready to move across the membrane and attach to the other kinase to be fully activated.

Movement across the membrane

The negatively charged phosphate groups on the cell membrane interact with the highly conserved positively charged residues on ALKAL ligand that face the membrane, which stabilizes the ligand to bind to ALK even better.

Disease

Relevance

Structural highlights

The active state of the kinase is when two monomers have completed a conformational change and moved across the membrane to form a .



Caption for this structure

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ReferencesReferences

  1. ↑ Reshetnyak AV, Rossi P, Myasnikov AG, Sowaileh M, Mohanty J, Nourse A, Miller DJ, Lax I, Schlessinger J, Kalodimos CG. Mechanism for the activation of the anaplastic lymphoma kinase receptor. Nature. 2021 Dec;600(7887):153-157. doi: 10.1038/s41586-021-04140-8. Epub 2021, Nov 24. PMID:34819673 doi:http://dx.doi.org/10.1038/s41586-021-04140-8

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

OCA, Jaime Prilusky, Andrew Peters, R. Jeremy Johnson, Hillary Kulavic
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