MadSci Network: Cell Biology
Query:

Re: What is a 'constitutive complex?'

Date: Mon Oct 29 14:55:26 2001
Posted By: Elena Rodriguez, Grad student, Molecular and Cell Biology, University of California, Berkeley
Area of science: Cell Biology
ID: 997071302.Cb
Message:

Well, instead of giving a definition of a constitutive complex, I think it 
would be better if we discussed the concept of a constitutive complex.
The word constitutive, means the signal (usually enzymatic activity) is 
"always on".  When something is always on, therefore, it is not regulated 
like a switch- turning on or turning off.
So, the term constitutive complex is refering to a protein complex (one or 
more protein subunits) bound together to have at least one enzymatic 
activity "always on". In the cell, constitutive complexes exisit in many 
different systems. For example, the translational machienery (the ribosome) 
is a constituative complex in that, as long as the mRNA and initiation 
factors are available, the ribosomal subunits will initiate translation- the 
translational machienery does not need to be "turned on", it is already on 
and ready to start translating.
In cellular signaling, however, switch-like activity is essential for 
creating transient, amplified resoponses to diverse signals. 
In order for the cell to repond quickly to a single external signal 
(ligand), for example, not only does the receptor that binds to that signal 
need to be turned on, but every member of the intracellular signaling 
cascade must be turned on (activated). As you may know, signaling cascades 
involving multiple enzymes were evolved to allow multiple points of 
amplification (such as the production of second messengers), so that a 
single binding event on the cell surface (the ligand with its receptor) can 
lead to a dramatic change within the cell.
But, not only do all these members of the cascade need to be turned on and 
activated, but they must also be turned off and repressed in a timely manner 
to create a TRANSIENT response.
In order to turn on each of these members protein complexes are formed to 
activate an enzyme. Any time any allosteric regulator binds to an enzyme and 
activates it is a "activated complex".  Many receptors, for example, have 
intracellular enzymatic activity and the receptor becomes activated upon 
binding to its ligand.
A Constituative complex in cellular signaling, therefore, is most likely a 
mutant. Cell biologists may use these constituatively-active mutants to 
study the effect of having a signaling cascade "always on".
Many times these mutants bind irreversibly to their acitvators, so that they 
are always on. One example of a constituative complex is a mutant of the 
small GTPase RAS. When Ras is bound to GTP it on, the V12 mutant of RAS is 
defective in it's GTPase activity so that it can't hydrolyze GTP to GDP and 
be turned off.
I hope this helps!
Elena Rodriguez




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