| Autor: |
Moonsoo Jin, Gang Song, Carman, Christopher V., Yong-Sung Kim, Astrof, Nathan S., Shimaoka, Motomu, Wittrup, Dane K., Springer, Timothy A. |
| Předmět: |
|
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 4/11/2006, Vol. 103 Issue 15, p5758-5763, 6p, 2 Diagrams, 2 Charts, 7 Graphs |
| Abstrakt: |
Understanding allostery may serve to both elucidate mechanisms of protein regulation and provide a basis for engineering active mutants. Herein we describe directed evolution applied to the integrin αL inserted domain for studying allostery by using a yeast surface display system. Many hot spots for activation are identified, and some single mutants exhibit remarkable increases of 10,000-fold in affinity for a physiological ligand, intercellular adhesion molecule-1. The location of activating mutations traces out an allosteric interface in the interior of the inserted domain that connects the ligand binding site to the α7-helix, which communicates allostery to neighboring domains in intact integrins. The combination of two activating mutations (F265S/F292G) leads to an increase of 200,000-fold in affinity to intercellular adhesion molecule-1. The F265S/F292G mutant is potent in antagonizing lymphocyte function-associated antigen 1-dependent lymphocyte adhesion, aggregation, and transmigration. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
