What is the SMALLEST DNA BINDING DOMAIN?

Kevin Gardner gardner at bloch
Mon Jan 13 11:59:38 EST 1997


(Followups trimmed)

Angeline Kantola (kantola at u.washington.edu) wrote:
: Cys2-His2 zinc fingers are on the order of 30 amino acids long. As the
: name suggests, a zinc atom is critical for structural integrity of the
: functional domain. Proteins which bind DNA via C2H2 zinc fingers do so
: sequence specifically.  There's no evidence that single zinc fingers bind
: nucleic acids, though. A minimum of three of these fingers are required to
: bind or, as in the case of yeast ADR1, two fingers and a non-finger N
: termial region.

: C2H2 zinc fingers are everywhere (there are other kinds of zinc fingers as
: well), 

And I'd like to bring up one of those other kinds of zinc fingers:
the Zn(2)Cys(6) binuclear cluster class, whose best known member is
the S. cerevisiae GAL4 transcriptional activator.  Somewhat similarly
to the Cys2-His2 group above, the part of the domain that binds DNA
and 2*Zn(II) is about 30aa in length and recognizes a 5'-CGG-3'
triplet.

This is somewhat of an oversimplification, though.  Similarly to the 
Cys2-His2 case, specificity is derived from using multiple domains;
in contrast, though, these domains are non-covalently dimerized, making
the spacing between two inverted CGG elements as the prime source
of specificity.  When you add the additional linker & dimerization
helix onto the DNA-binding domain, the total length kicks up to ca.
50-60aa.

References:
aside from my own work (NMR studies of GAL4 and LAC9, a K. lactis
GAL4 homologue :), I'd check into:

	*specificity: several recent papers by Aseem Ansari in 
		Mark Ptashne's group and references therein.
		
	*sequence homology in group: alignment paper in NAR last
		month (NAR 24(1996): 4599-4607)
		
	*structural biology: two crystal structures of protein
		DNA/complexes by Ronan Marmorstein when he was
		in Steve Harrison's group (GAL4 and PPR1); additional
		NMR studies by several groups including Gerhard Wagner,
		Ernest Laue, Joe Coleman and others.
		
Cheers,
Kevin

--
*************************************************************************
Kevin Gardner                               gardner at bloch.med.utoronto.ca
University of Toronto             http://abragam.med.utoronto.ca/~gardner
Dept. of Medical Genetics & Microbiology   phone: 416-978-0642/FAX: -6885



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