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DNA --> RNA --> protein
major dogma
constant production
regulate transcription
degrade RNA
regulate translation
regulate enzyme activity
degrade protein
major modes of regulation
constant poduction
constitutive proteins are needed at the same level at all times
regulate transcription and enzyme activity
two most important modes of regulation
regulation of transcription
post-translational regulation
two major levels of regulation in the cell
regulation of transcription
major; regulates amount of a protein; slower (minutes)
regulation of translation
similar to regulation of transcription but is minor
post-translational regulation
regulate activity of preexisiting proteins; very fast (seconds)
DNA binding proteins
atoms involved in protein-DNA interaction
requires regulatory sequences that are many times adjacent to the promoter
transcription
DNA binding proteins are central to regulation of
helix-turn-helix motif
one of the most common DBP
two per monomer
nonpolar forces between helices stabilize motif
regulation helix
first helix in the helix-turn-helix motif that forms H bonds with bases in the major groove
major groove
main site of protein binding on the DNA
stabilizing helix
second helix in the helix-turn-helix motif
zinc finger
leucine zipper
other common DBP
inverted repeats
frequently are binding sites for homodimeric regulatory proteins
small molecules
influence the binding of regulatory proteins to DNA through allosteric interactions, covalent modifications, etc.
zinc fingers
contain protein structure that binds a Zn ion
three can bind to DNA
leucine zippers
leucine residues are spaced every 7 amino acids and interact to form a homodimer
blocking or activation of transcription
DNA binding by a protein can lead to
operator
the piece of DNA that overlaps the promoter site and serves as the on-off switch
activator-binding site
nucleotide sequence that precedes an ineffective promoter
does not have to be adjacent to promoter
thought to change DNA conformation
operon
composed of binding sites, genes, and regulatory elements
promoter
can be strong or weak
can bind dominant or alternaive sigma factors
repressor
homodimeric DBP
negative control
regulatory mechanism that stops transcription
repression
induction
types of negative control
repression (arg operon)
repressor inactive (not bound to signal)
cannot bind to operator
transcription proceeds
repressor active (bound to signal)
binds to operator
blocks transcription
induction (lac operon)
repressor active (not bound to signal)
binds to operator
blocks transcription
repressor inactive (bound to signal)
cannot bind to operator
transcription
LacI
lac operon repressor
repression
preventing synthesis of an enzyme in response to a signal (bound --> active)
anabolic enzymes
enzymes not synthesized when not needed
induction
synthesis is prevented in absence of a signal (not bound --> active)
catabolic enzymes
enzymes synthesized only when needed
activation
form of positive control
activation (mal operon)
activator inactive (not bound to signal)
cannot bind to activator binding site
no transcription
activator active (bound to signal)
binds to activator binding site
transcription
MalT
mal operon activator
activator protein
helps RNAP recognize promoter
may cause change in DNA structure
may interact directly with RNAP
regulon
multiple operons controlled by same regulatory protein
positive and negative control
maltose regulon
has 4 maltose operons under control of same activator
global regulation
simultaneous regulations of many different genes
CRP
cAMP receptor protein
global regulatory element
functions as activator protein in lac operon, needed in active form for transcription
catabolite repression
not using the less energetic carbon source
glucose
inhibits activity and synthesis of cAMP by inhibiting adenylate cyclase
cAMP cannot bind to and activate CRP
no transcription
transcription proceeds
CRP and lactose in lac operon
no transcription
glucose present (no active CRP) and lactose absent (repression) in lac operon
low expression
glucose present (no active CRP) and lactose present (no repression) in lac operon
transcription proceeds
glucose absent (cAMP, active CRP) and lactose present (no repression) in lac operon
flagellar genes
controlled by catabolite repression
cAMP
key molecule in many metabolic control systems
derived from nucelic acid percursor
NrpR blocks TFB and TBP binding (no transcription)
NrpR binds alpha-ketoglutarate
NrpR released, TFB and TBP bind (transcription)
regulation of N metabolism in Archaea
Pyrococcus furiosus
uses a single regulatory protein to switch between fermentation and sulfur reduction
no sulfur --> active, activates transcription of hydrogenase which represses transcription
sulfur --> inactive (oxidized)
NrpR
example of archaeal repressor protein from Methanococcus moripaludis
Note 
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