Alternating zinc-finger motifs in the human male-associated protein ZFY.
ZFY, a putative transcription factor encoded by the human Y chromosome, contains a distinctive two-finger repeat: odd-numbered and even-numbered CC/HH metal-binding motifs exhibit systematic alternation in sequence pattern. Such alternation, which is not generally observed in zinc-finger proteins, has also been described in an extensive family of Kruppel-like genes in Xenopus laevis and in the AIDS-associated human DNA-binding protein HIV-EP1. The strict conservation of a two-finger repeat among ZFY-, Kruppel- and HIV-related zinc-finger proteins suggests distinct mechanisms of protein-nucleic acid recognition. To test whether this sequence pattern reflects an underlying alternation in domain structure, we have synthesized and characterized single-finger peptides from the human ZFY gene. Remarkably, systematic differences in metal-dependent folding are observed in the circular dichroism spectra of even- and odd-numbered domains. Our results suggest the existence of distinct CC/HH finger submotifs, which may play different roles in nucleic acid recognition.
Weiss
M A
MA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Mason
K A
KA
Dahl
C E
CE
Keutmann
H T
HT
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D002942:Circular Dichroism; D003035:Cobalt / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008667:Metalloproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D008667:Metalloproteins; D014157:Transcription Factors; C054430:ZFY protein, human; D003035:Cobalt; D015032:Zinc