title: Effects of actin-binding proteins on the thermal stability of monomeric actin.
abstract: Differential scanning calorimetry (DSC) was applied to investigate the thermal unfolding of rabbit skeletal muscle G-actin in its complexes with actin-binding proteins, cofilin, twinfilin, and profilin. The results show that the effects of these proteins on the thermal stability of G-actin depend on the nucleotide, ATP or ADP, bound in the nucleotide-binding cleft between actin subdomains 2 and 4. Interestingly, cofilin binding stabilizes both ATP-G-actin and ADP-G-actin, whereas twinfilin increases the thermal stability of the ADP-G-actin but not that of the ATP-G-actin. By contrast, profilin strongly decreases the thermal stability of the ATP-G-actin but has no appreciable effect on the ADP-G-actin. Comparison of these DSC results with literature data reveals a relationship between the effects of actin-binding proteins on the thermal unfolding of G-actin, stabilization or destabilization, and their effects on the rate of nucleotide exchange in the nucleotide-binding cleft, decrease or increase. These results suggest that the thermal stability of G-actin depends, at least partially, on the conformation of the nucleotide-binding cleft: the actin molecule is more stable when the cleft is closed, while an opening of the cleft leads to significant destabilization of G-actin. Thus, DSC studies of the thermal unfolding of G-actin can provide new valuable information about the conformational changes induced by actin-binding proteins in the actin molecule.
authors.affiliation: A. N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect 33, Moscow 119071, Russian Federation.
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Pivovarova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Chebotareva
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kremneva
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
authors.forename: Dmitrii I
authors.initials: DI
authors.lastname: Levitsky
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002152:Calorimetry, Differential Scanning; D008840:Microfilament Proteins / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism; D055503:Protein Multimerization; D055550:Protein Stability; D058767:Protein Unfolding; D011817:Rabbits; D013696:Temperature
chemical_list: C042634:ADP-G-actin; C022920:ATP-G-actin; D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D051304:Profilins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate