Functional interference between contacting amino acids of homeodomains

FEBS Letters
L PellizzariG Damante

Abstract

In a protein, the function of an amino acid at some position depends on the amino acids at other positions. Here we demonstrate a functional interference between base-contacting amino acids (at positions 50 and 54) of homeodomains. When, in the context of Antennapedia or Goosecoid homeodomains, Lys50 is paired to Tyr54 or Ala54 and Gln50 is paired to Met54, the resulting proteins efficiently discriminate among different DNA sequences. In contrast, in the presence of the pair Lys50-Met54, both homeodomains show a reduced capability to discriminate among different DNA sequences. Sequence selection experiments performed in the context of the Goosecoid homeodomain suggest that the presence of Met54 precludes the base-discriminating function of Lys50. These results may explain why the pair Lys50-Met54 is never found in natural homeodomains.

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Citations

Oct 12, 2001·Brain Research Bulletin·L Kammermeier, H Reichert
Jun 1, 2002·Gene·Fedor EroshkinAndrey Zaraisky
Jul 5, 2012·The Journal of Biological Chemistry·E Aaron RunkleDavid Mu
Oct 29, 1999·DNA and Cell Biology·M L TejadaR G Deeley
Sep 26, 2000·Molecular and Cellular Biology·V DaveJ Ma
Jan 13, 2006·Journal of Molecular Biology·Jamie M Baird-TitusMark Rance
Jun 9, 2006·Differentiation; Research in Biological Diversity·Salvatore D'AnielloMargherita Branno
Oct 12, 2000·The Journal of Biological Chemistry·R H Harrington, A Sharma
Mar 4, 2011·Molecular Biology Reports·Cinzia PuppinGiuseppe Damante

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