Alternating zinc fingers in the human male associated protein ZFY: Refinement of the NMR structure of an even finger by selective deuterium labeling and implications for DNA recognition

Journal Article · Tue Jul 23 04:00:00 EDT 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00243a005· OSTI ID:5013793

Kochoyan, M ^[1]; Keutmann, H T; Weiss, M A ^[2]

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1. Harvard Medical School, Boston, MA (United States)
2. Massachusetts General Hospital, Boston (United States)

ZFY, a male-associated Zn-finger protein encoded by the human Y chromosome, exhibits a distinctive two-finger repeat: whereas odd-numbered domains fit a general consensus, even-numbered domains exhibit systematic differences. Do these odd and even sequences encode structurally distinct surfaces for DNA recognition As a first step toward answering this question, the authors have recently described the sequential {sup 1}H NMR assignment of a representative nonconsensus Zn finger (designated AFY-6T) based on 2D NMR studies of a 30-residue peptide. Initial structural modeling by distance geometry/simulated annealing (DG/SA) demonstrated that this peptide retained the N-terminal {beta}-hairpin and C-terminal {alpha}-helix ({beta}{beta}{alpha} motif) observed in consensus Zn fingers. However, the precision of this initial structure was limited by resonance overlap, which led to ambiguities in the assignment of key NOEs in the hydrophobic core. In this paper these ambiguities are resolved by selective deuterium labeling, enabling a refined structure to be calculated by DG/SA and restrained molecular dynamics. These calculations provide a detailed view of the hydrophobic core and protein surface, which are analyzed in reference to previously characterized Zn fingers.

• OSTI ID: 5013793
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:29; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BARYONS
CHROMOSOMES
DEUTERIUM COMPOUNDS
DNA
DNA SEQUENCING
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HETEROCHROMOSOMES
HUMAN Y CHROMOSOME
HYDROGEN COMPOUNDS
MAGNETIC RESONANCE
MAMMALS
MAN
MOLECULAR STRUCTURE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
ORGANIC COMPOUNDS
OVERHAUSER EFFECT
PRIMATES
PROTEINS
PROTONS
RESONANCE
STEREOCHEMISTRY
STRUCTURAL CHEMICAL ANALYSIS
TRANSCRIPTION
VERTEBRATES
Y CHROMOSOME
ZINC COMPOUNDS