Alternating zinc fingers in the human male associated protein ZFY: 2D NMR structure of an even finger and implications for jumping-linker DNA recognition
- Harvard Medical School, Boston, MA (USA)
- Massachusetts General Hospital, Boston, MA (USA)
- Harvard Medical School, Boston, MA (USA) Massachusetts General Hospital, Boston (USA)
ZFY, a sex-related Zn-finger protein encoded by the human Y chromosome, is distinguished from the general class of Zn-finger proteins by the presence of a two-finger repeat. Whereas odd-numbered domains and linkers fit a general consensus, even-numbered domains and linkers exhibit systematic differences. Because this alternation may have fundamental implications for the mechanism of protein-DNA recognition, the authors have undertaken biochemical and structural studies of fragments of ZFY. They describe here the solution structure of a representative nonconsensus (even-numbered) Zn finger based on 2D NMR studies of a 30-residue peptide. Structural modeling by distance geometry and simulated annealing (DG/SA) demonstrates that this peptide folds as a miniglobular domain containing a C-terminal {beta}-hairpin and N-terminal {alpha}-helix ({beta}{beta}{alpha} motif). These features are similar to (but not identical with) those previously described in consensus-type Zn fingers (derived from ADR1 and Xfin); the similarities suggest that even and odd ZFY domains bind DNA by a common mechanism. A model of the protein-DNA complex (designated the jumping-linker model) is presented and discussed in terms of the ZFY two-finger repeat. In this model every other linker is proposed to cross the minor groove by means of a putative finger/linker submotif HX{sub 4}HX{sub 3}-hydrophobic residue-X{sub 3}.
- OSTI ID:
- 5464637
- Journal Information:
- Biochemistry; (United States), Vol. 30:14; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HUMAN Y CHROMOSOME
GENE REGULATION
TRANSCRIPTION FACTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
MAN
NUCLEAR MAGNETIC RESONANCE
PROTEIN STRUCTURE
ANIMALS
CHROMOSOMES
HETEROCHROMOSOMES
MAGNETIC RESONANCE
MAMMALS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RESONANCE
VERTEBRATES
Y CHROMOSOME
550200* - Biochemistry