 |
PDBsum entry 6ntp
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Minimally disruptive optical control of protein tyrosine phosphatase 1b.
|
|
|
Authors
|
|
A.Hongdusit,
P.H.Zwart,
B.Sankaran,
J.M.Fox.
|
|
|
Ref.
|
|
Nat Commun, 2020,
11,
788.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Protein tyrosine phosphatases regulate a myriad of essential subcellular
signaling events, yet they remain difficult to study in their native biophysical
context. Here we develop a minimally disruptive optical approach to control
protein tyrosine phosphatase 1B (PTP1B)-an important regulator of receptor
tyrosine kinases and a therapeutic target for the treatment of diabetes,
obesity, and cancer-and we use that approach to probe the intracellular function
of this enzyme. Our conservative architecture for photocontrol, which consists
of a protein-based light switch fused to an allosteric regulatory element,
preserves the native structure, activity, and subcellular localization of PTP1B,
affords changes in activity that match those elicited by post-translational
modifications inside the cell, and permits experimental analyses of the
molecular basis of optical modulation. Findings indicate, most strikingly, that
small changes in the activity of PTP1B can cause large shifts in the
phosphorylation states of its regulatory targets.
|
|
|
|
|
|
|
