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A similar situation is found in the external scaffolding protein D of
bacteriophage phiX174.
This protein associates as dimers and tetramers, upon which assembly
stops. (The tetramer is the assembly-active unit.) The situation is a
little different, since the dimer also does not have 2f symmetry. In
this case, a conformational change (shift from a straight to a bend
helix) prevents the assembly of the dimers into a helix. Two of those
asymmetric dimers then associate via different interactions. Another
conformational change prevents the tetramer from adding any further
dimers.
See
Dokland et al 1997 Nature 389, 308-313
Dokland et al 1999 JMB 288, 595-608
and
Morais et al 2004 Mol Cell 15, 991-997
Hope this is useful
Terje
On Aug 26, 2005, at 10:06 AM, Nicholas M Glykos wrote:
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Dear All,
Imagine a homodimeric protein. Let's say, this one (dyad shown) :
|
_od|do\.
.d*'' | ""&\
,H' | *b
H| | H,
-M | ||
M. | ]|
4L | .M
H, | H|
`M | |F
?b | ,H
9? | .H'
`H, | d|
`H,| J?
`#|&?
|
|
Imagine that there is conclusive experimental evidence that this
homodimer
forms homotetramers like this one :
,op=d=po_
o&'' ``&\
d? 9? __,\\_
.R M. _dd"""`"`*b.
|[ &| d*' `H\
`M. M:H' `M.
9| ?TH| .M
`M. ,H>T J}
|H H\H- dP
TL d?JT ,H'
H, ,P.M- ,&*
`H, ,H'J} .?&'
`H. ,H'.M _#*"
`*#*' |P .o&''
|L_op*"
`'"
The problem is that oligomerisation stops there : although there are
two
putative dimerisation interfaces available (in the homotetramer), and
although there would be no steric clashes from the addition of further
homodimers, it doesn't happen (solution evidence from analytical
ultracentrifugation and gel filtration, crystal structures).
We have tried to wave off the question by (i) invoking 'some kind of
allosteric effect kicking-in upon tetramer formation', and, (ii) by
imagining 'an electrostatic effect' which would not require significant
structural changes upon tetramer formation (although I intuitively
imagine
that this electrostatics explanation is inconsistent with the symmetry
of
association).
Any thoughts (or related literature) on the subject will be gratefully
received,
Best regards,
Nicholas
--
Dr Nicholas M. Glykos, Department of Molecular
Biology and Genetics, Democritus University of Thrace,
Dimitras 19, 68100 Alexandroupolis, GREECE, Fax ++302551030613
Tel ++302551030620 (77620), http://www.mbg.duth.gr/~glykos/
---
Terje Dokland, PhD
Associate Professor
Department of Microbiology
University of Alabama at Birmingham
845 19th St South, BBRB 311
Birmingham, AL 35294
Tel : 205-996 4502
Fax: 205-996 2667
"Convictions are greater enemies of truth than lies"
-- Nietzsche
