5ZNF

ALTERNATING ZINC FINGERS IN THE HUMAN MALE ASSOCIATED PROTEIN ZFY: 2D NMR STRUCTURE OF AN EVEN FINGER AND IMPLICATIONS FOR "JUMPING-LINKER" DNA RECOGNITION

Summary for 5ZNF

• Entry DOI: 10.2210/pdb5znf/pdb
• Descriptor: ZINC FINGER, ZINC ION (2 entities in total)
• Functional Keywords: zinc finger dna binding domain
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P08048
• Total number of polymer chains: 1
• Total formula weight: 3680.49

Authors

Kochoyan, M.,Keutmann, H.T.,Weiss, M.A. (deposition date: 1991-08-22, release date: 1994-01-31, Last modification date: 2024-05-22)

Primary citation

Kochoyan, M.,Havel, T.F.,Nguyen, D.T.,Dahl, C.E.,Keutmann, H.T.,Weiss, M.A.
Alternating zinc fingers in the human male associated protein ZFY: 2D NMR structure of an even finger and implications for "jumping-linker" DNA recognition.
Biochemistry, 30:3371-3386, 1991

PubMed Abstract: 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, we have undertaken biochemical and structural studies of fragments of ZFY. We 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 HX4HX3-hydrophobic residue-X3. Analogous use of a hydrophobic residue in a linker that spans the minor groove has recently been described in crystallographic and 3D NMR studies of homeodomain-DNA complexes. The proposed model of ZFY is supported in part by the hydroxyl radical footprint of the TFIIIA-DNA complex [Churchill, M.E.A., Tullius, T.D., & Klug, A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5528-5532].

PubMed: 1849423
DOI: 10.1021/bi00228a004

Experimental method

SOLUTION NMR