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The X‐ray structure of an atypical homeodomain present in the rat liver transcription factor LFB1/HNF1 and implications for DNA binding.
Author(s) -
Ceska T.A.,
Lamers M.,
Monaci P.,
Nicosia A.,
Cortese R.,
Suck D.
Publication year - 1993
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1993.tb05828.x
Subject(s) - computer science
The transcription factor LFB1/HNF1 from rat liver nuclei is a 628 amino acid protein that functions as a dimer binding to the inverted palindrome GTTAATN‐ATTAAC consensus site. We have crystallized a 99 residue protein containing the homeodomain portion of LFB1, and solved its structure using X‐ray diffraction data to 2.8 A resolution. The topology and orientation of the helices is essentially the same as that found in the engrailed, MAT alpha 2 and Antennapedia homeodomains, even though the LFB1 homeodomain contains 21 more residues. The 21 residue insertion is found in an extension of helix 2 and consequent lengthening of the connecting loop between helix 2 and helix 3. Comparison with the engrailed homeodomain‐DNA complex indicates that the mode of interaction with DNA is similar in both proteins, with a number of conserved contacts in the major groove. The extra 21 residues of the LFB1 homeodomain are not involved in DNA binding. Binding of the LFB1 dimer to a B‐DNA palindromic consensus sequence requires either a conformational change of the DNA (presumably bending), or a rearrangement of the subunits relative to the DNA.