Details

Autor(en) / Beteiligte

• Yao, Xiaoyi
• Grade, Stephanie
• Wriggers, Willy
• Rubenstein, Peter A.

Titel

His73, Often Methylated, Is an Important Structural Determinant for Actin

Ist Teil von

• The Journal of biological chemistry, 1999-12, Vol.274 (52), p.37443-37449

Ort / Verlag

American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

1999

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• His 73 , has been proposed to regulate the release of P i from the interior of actin following polymerization-dependent hydrolysis of bound ATP. Although it is a 3-methylhistidine in the vast majority of actins, His 73 is unmethylated in S. cerevisiae actin. We mutated His 73 in yeast actin to Arg, Lys, Ala, Gln, and Glu and detected no altered phenotypes associated with the mutations in vivo . However, they significantly affect actin function in vitro . Substitution of the more basic residues resulted in enhanced thermal stability, decreased rate of nucleotide exchange, and decreased susceptibility to controlled proteolysis relative to wild-type actin. The opposite effects are observed with the neutral and anionic substitutions. All mutations reduced the rate of polymerization. Molecular dynamics simulations predict a new conformation for the His 73 imidazole in the absence of a methyl group. It also predicts that Arg 73 tightens and stabilizes the actin and that Glu 73 causes a rearrangement of the bottom of actin's interdomain cleft leading possibly to our observed destabilization of actin. Considering the exterior location of His 73 , this work indicates a surprisingly important role for the residue as a major structural determinant of actin and provides a clue to the impact caused by methylation of His 73 .