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Thymosin beta4 induces a conformational change in actin monomers.

Authors :
Dedova IV
Nikolaeva OP
Safer D
De La Cruz EM
dos Remedios CG
Source :
Biophysical journal [Biophys J] 2006 Feb 01; Vol. 90 (3), pp. 985-92. Date of Electronic Publication: 2005 Nov 04.
Publication Year :
2006

Abstract

Using fluorescence resonance energy transfer spectroscopy we demonstrate that thymosin beta(4) (tbeta(4)) binding induces spatial rearrangements within the small domain (subdomains 1 and 2) of actin monomers in solution. Tbeta(4) binding increases the distance between probes attached to Gln-41 and Cys-374 of actin by 2 A and decreases the distance between the purine base of bound ATP (epsilonATP) and Lys-61 by 1.9 A, whereas the distance between Cys-374 and Lys-61 is minimally affected. Distance determinations are consistent with tbeta(4) binding being coupled to a rotation of subdomain 2. By differential scanning calorimetry, tbeta(4) binding increases the cooperativity of ATP-actin monomer denaturation, consistent with conformational rearrangements in the tbeta(4)-actin complex. Changes in fluorescence resonance energy transfer are accompanied by marked reduction in solvent accessibility of the probe at Gln-41, suggesting it forms part of the binding interface. Tbeta(4) and cofilin compete for actin binding. Tbeta(4) concentrations that dissociate cofilin from actin do not dissociate the cofilin-DNase I-actin ternary complex, consistent with the DNase binding loop contributing to high-affinity tbeta(4)-binding. Our results favor a model where thymosin binding changes the average orientation of actin subdomain 2. The tbeta(4)-induced conformational change presumably accounts for the reduced rate of amide hydrogen exchange from actin monomers and may contribute to nucleotide-dependent, high affinity binding.

Details

Language :
English
ISSN :
0006-3495
Volume :
90
Issue :
3
Database :
MEDLINE
Journal :
Biophysical journal
Publication Type :
Academic Journal
Accession number :
16272441
Full Text :
https://doi.org/10.1529/biophysj.105.063081