Domains and motifs

Kevin Gardner gardner at bloch
Tue Jan 14 15:26:28 EST 1997


Hi all:
	While my upstairs neightbor Larry (lamoran at gpu.utcc.utoronto.ca) 
brings up an interesting point in this discussion, I think we're on two 
different wavelengths on the definition of domains and motifs.  Anyone 
else care to comment?

L.A. Moran (lamoran at gpu.utcc.utoronto.ca) wrote:
: This request brings up another issue that might be worth discussing. Should
: these DNA binding regions be referred to as "domains" or "motifs"? In the
: literature on protein structure the word "domain" usually refers to a
: discrete, independently folding region with a globular structure. Such
: domains consist of large stretches of primary sequence and they can be
: recognized as distinct units in the overall structure of a protein. Domains
: are usually connected by short linker sequences.

OK --- looks good so far, although I don't agreed with the term "large
stretches" of primary sequence.  Some domains that don't bind ligands
are as small as ~50-60 aa (SH3 domain, for example); if metals and/or
disulfide bonds are present, the size can be smaller.

: Domains, as defined by structural biologists, consist of multiple regions
: of secondary or supersecondary structures.

Fine.

: Zinc fingers and other zinc containing structures are examples of motifs
: and not, strictly speaking, domains. They are often part of a large domain
: within a protein. Motifs are usually short stretches of primary sequence
: on the order of 20-100 amino acid residues. Domains are larger.

Whoa --- speaking as a structural biologist who has worked on DNA-binding
domains such as these, I don't agree with this assessment.  The
Cys(2)His(2) canonical zinc finger and the GAL4/Cys(6) both fall into
a domain by your criteria that you initially listed: discrete, 
independently-folding regions with globular structures.  They're connected
to other domains by linker regions, and both have multiple regions of
secondary structure (2 strands of beta sheet and a helix for the
Cys(2)His(2), 2 helices for GAL4).  Yes, these domains require metal
ion(s) in order to assume their folded, active state.  

Given this above information, I'd be interested in hearing how these
would fail to be considered domains.  Yes, they are small domains 
(as asked for), but I believe they meet the appropriate criteria.

: Some people are very sensitive about the naming of zinc containing structures.
: The C2H2 structure is called a zinc finger but the others are not referred
: to as "fingers". It is probably useful to maintain this distinction.

Being one of those people who's worked on the naming of zinc-containing
structures that isn't a Cys(2)His(2) domain, I'd like to see this
distinction maintained.  But I also realized that the chances of this
happening are essentially nil....

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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