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Structural studies of the engrailed homeodomain
Author(s) -
Clarke Neil D.,
Kissinger Charles R.,
Desjarlais John,
Gilliland Gary L.,
Pabo Carl O.
Publication year - 1994
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560031018
Subject(s) - engrailed , dihedral angle , homeobox , protein structure , chemistry , crystallography , amino acid , helix (gastropod) , side chain , dna , stereochemistry , biology , biochemistry , gene , molecule , transcription factor , hydrogen bond , ecology , organic chemistry , snail , polymer
The structure of the Drosophila engrailed homeodomain has been solved by molecular replacement and refined to an R ‐factor of 19.7% at a resolution of 2.1 Å. This structure offers a high‐resolution view of an important family of DNA‐binding proteins and allows comparison to the structure of the same protein bound to DNA. The most significant difference between the current structure and that of the 2.8‐Å engrailed‐DNA complex is the close packing of an extended strand against the rest of the protein in the unbound protein. Structural features of the protein not previously noted include a “herringbone” packing of 4 aromatic residues in the core of the protein and an extensive network of salt bridges that covers much of the helix 1‐helix 2 surface. Other features that may play a role in stabilizing the native state include the interaction of buried carbonyl oxygen atoms with the edge of Phe 49 and a bias toward statistically preferred side‐chain dihedral angles. There is substantial disorder at both ends of the 61 amino acid protein. A 51‐amino acid variant of engrailed (residues 6–56) was synthesized and shown by CD and thermal denaturation studies to be structurally and thermodynamically similar to the full‐length domain.