Chapter 11: Translation Flashcards
production of a protein from the information in an mRNA
translation
provides the physical link that decodes mRNA into protein
tRNA (transfer RNA)
tRNAs read the mRNA by base-pairing 3 nucleotides: region in tRNA is the (1), while the region on the mRNA is the (2)
- anticodon
- codon
amino acids are attached to tRNAs by ()
aminoacyl-tRNA synthetases
Protein synthesis is carried out by a large molecular machine ()
ribosome
ribosomes have ()
2/3 RNA (rRNA) + 1/3 protein (r-proteins)
the (1) subunit of the ribosome deciphers the mRNA and the (2) subunit mediates the chemical bond formation
- small
- large
ribosomes move () along an mRNA molecule
processively (5’ to 3’)
Proteins are synthesized at a rate of about (1) amino acids per second, with
an error rate of about (2) per residue
- 15
- 10-3 to 10-4
translation factors are often () that use the energy of () hydrolysis
GTPases, GTP
4 main stages of translation
- initiation
- elongation
- termination
- ribosome recycling
two essential processes of transfer RNAs (tRNAs)
- decipher mRNAs
- carry amino acids
(): tRNA structure has four regions of double-stranded RNA, including 3 stem-loops
clover-leaf pattern
2D structure of tRNA: 5’ and 3’ ends base pair and form the (1), with a conserved (2), which is the attachment point of the amino acid
- acceptor stem
- 3’ CCA tail
2D structure of tRNA: the () has 3 nucleotides that base pair with the codon in mRNA in an antiparallel fashion
anticodon loop
a folded tRNA has an () structure (3D)
L-shape
the bases in a tRNA anticodon (position 34-36) are typically stacked on top of each other in a structure called a () -> anticodon loop positions the nucleotides to effectively base pair with mRNA
U-turn
A () (e.g. base Y) occurs just after the anticodon (typically position 37, found in anticodon loop), to prevent this from base-pairing with the codon in mRNA.
hypermodified purine
hypermodified purine after the anticodon aligns the codon and anticodon properly -> critical for ensuring high fidelity of ()
decoding
in tRNA, () is typically in position 34 (in anticodon loop) is important for wobble pairing
inosine
the DHU (D) loop in tRNA is named after the () in the loop
dihydrouridine (D)
the TpsiC (T) loop has (1) and (2) in the T loop
- ribothymidine (T)
- pseudouridine (psi)
Each triplet codon specifies a single amino acid (1) or no amino acid (2).
- sense codon
- stop codon; nonsense codon
() codons signal the end of the protein-coding region of the mRNA
stop
Different tRNAs that carry the same amino acids are called ()
isoacceptors
the first 2 positions on the mRNA (reading 5’ to 3’) are read by () with positions 2 and 3 of the anticodon
strict Watson-Crick base pairing
in the 3rd position of the codon (interacts with position 1 of the anticodon) pairing deviations are allowed -> called ()
wobble pairing
consequences of wobble pairing
- allows some non-Watson-Crick interactions
- same tRNA can interpret both CUC and CUU
- not each codon needs its own tRNA
some codons are used more infrequently than others -> called (); tend to be decoded by rarer tRNAs
rare codons
the genetic code is almost () in all organisms
the same; nearly universal
AUG usually codes for ()
methionine
there are usually 3 stop codons
UAA, UAG, UGA
evolution has conserved codons so that mutations that change the encoded amino acid usually result in ()
a chemically similar amino acid
() is a process that attaches amino acids to tRNAs
aminoacylation
in the first step of aminoacylation, the amino acid is activated by the attachment of (1) to form an (2)
- AMP
- aminoacyl adenylate
in the second step of aminoacylation, the enzyme (aaRS) then transfers the amino acid to the () of the terminal adenosine on the tRNA 3’ CCA tail
2’ or 3’ OH of the ribose
resulting product of aminoacylation is ()
aminoacyl-tRNA
Resulting aminoacyl-tRNA is protected from spontaneous hydrolysis by immediate binding of (1) in bacteria or (2) in eukaryotes
- EF-Tu
- eEF1A
Each amino acid has its own aminoacyl-tRNA synthetase -> The enzyme for a certain amino acid is denoted ()
aaRS, e.g. GlyRS
correct amino acid for a tRNA is referred to as ()
cognate
Aminoacyl-tRNA synthetases recognize tRNAs by sequence and structural features called (1) found primarily in the (2) and (3).
- identity elements
- anticodon loop
- acceptor stems
Aminoacyl-tRNA synthetases use various chemical features to discriminate btw different amino acids.
charge, hydrophobicity, size, shape
the correct amino acids are chosen in a ()-step process
two
Most aminoacyl-tRNA synthetases have an (1) site and an (2) site (where hydrolytic reaction takes place), which combine to recognize the correct amino acid
- aminoacylation
- editing
() keeps non-cognate amino acids that are too big out of the aminoacylation site
Size exclusion
The editing site can accommodate the activated amino acid prior to the transfer of the activated a.a. to the tRNA ()
editing pre-transfer
if an amino acid is rejected pre-transfer, the aminoacyl adenylate (activated amino acid) itself is ()
hydrolyzed
The editing site can accommodate the amino acid after attachment to the tRNA ()
editing post-transfer
If rejection occurs post-transfer, the amino acid is ()
cleaved from the tRNA
Cognate aminoacyl-adenylates or aminoacyl-tRNAs (can/cannot) enter the editing site and therefore (are, are not) edited.
cannot, are not
There are two classes of aminoacyl-tRNA synthetases, (), each with ~ 10 members
class I and II
Class I aminoacyl-tRNA synthetases usually recognize the (1) of the acceptor stem, class II the (2)
- minor groove
- major groove
Class I attaches amino acids to the (1) of the terminal ribose, class II to the (2).
- 2′ OH
- 3’ OH
Some bacteria and archaea have fewer than 20 synthetases–usually those for attaching () are the ones missing
glutamine and asparagine
A () changes the side chain of the attached amino acid from an acid to an amide, producing asparagine and glutamine-bound tRNAs
transamidase reaction
the large ribosomal subunit has an (1) through which the growing polypeptide emerges -> often a target for (2)
- exit tunnel
- antibiotics
eukaryotic and bacterial ribosomes are generally conserved but differ in their ()
composition
the () between the ribosomal subunits (where tRNA substrates bind and function) is rich in rRNA and poor in proteins
interface
on the () of the ribosome, ribosomal proteins are more evenly distributed
exterior
unusual structures of ribosomal proteins
- globular domains (in exterior)
- long extended arms (into core rRNA regions)
long extended arms of ribosomal proteins are usually () amino acids
highly basic
ribosome composition differs with ()
phylogeny
additional protein and RNA layers called () are found with increasing organism complexity
expansion segments
rRNAs in the ribosomal subunits are divided into () based on secondary structure
distinct domains
the ()S rRNA has 3 major and 1 minor domains
16S (18S in euks)
the ()S rRNA has 6 domains
23S (28S in euks)
organization of rRNA domains in the 2 subunits are different:
- in the small subunit, the domains are (1)
- in the large subunit, the domains are (2)
- discrete
- interwoven
the large subunit in bacterial ribosomes has a second RNA called the (1); eukaryotes have an additional (2) RNA
- 5S RNA
- 5.8S
ribosomal RNAs and proteins are () across species
extremely highly conserved
() are the crucial parts of ribosomes -> were present before other components, which were added later in evolution
RNAs
tRNAs bind successively at 3 sites within the ribosome
- aminoacyl (A) site
- peptidyl (P) site
- exit (E) site
in translation initiation, the first step is the identification of the (1)
AUG initiation codon
the AUG initiation codon is recognized by (1), the ribosome, and (2)
- initiation factors (IFs)
- special initiator methionine tRNA
Early initiation involves the (1) ribosomal subunit, and then the (2) subunit joins the complex
- small
- large
early initiation results in a ribosome with () bound in the P site
methionine-loaded tRNA
3 major steps of elongation (translation cycle)
- decoding at the A site
- catalysis of peptide bond formation
- translocation
during decoding at the A site, () loads the next charged tRNA into the A site, according to the codon on the mRNA
elongation factor Tu (in bacteria)
eEF1A in eukaryotes
EF-Tu/eEF1A loads aminoacyl-tRNAs into the ribosome through ()
GTP hydrolysis
() in cells are always complexed with EF-Tu for protection of the linkage between the amino acid and the tRNA from hydrolysis
free aminoacyl-tRNAs
peptide bond formation is catalyzed between ()
amino acids at the P and A sites
catalysis of peptide bond formation results in the transfer of the growing polypeptide to the tRNA–called ()– in the A site
peptidyl-tRNA
during translocation, () promotes the movement of the mRNA-tRNA through the ribosome
EFG (in bacteria)
EF2 (in eukaryotes)
action of EFG/EF2 moves the peptidyl-tRNA that was in the A site into the P site and brings a ()
new codon into the A site
after a new codon is brought to the A site, the tRNA in the () leaves the codon
E site
termination of translation occurs when the ribosome reaches a ()
stop codon
stop codons are recognized by (), not tRNAs
class I release factors
bacterial RF1 recognizes ()
UAA and UAG
bacterial RF2 recognizes ()
UAA and UGA
eukaryotic release factor () recognizes all 3 stop codons
eRF1
interaction between class I release factors and stop codons promotes ()
release of polypeptide from the ribosome
in addition to class I release factors, () are also involved in termination of the translation cycle
class 2 release factors
class 2 release factors are also ()
GTPases
examples of class 2 release factors
RF3 in bacteria
eRF3 in eukaryotes
large and small subunits of the ribosome dissociate and release the remaining tRNA nd mRNA
ribosome recycling
in bacteria, () help in dissociation of ribosome during recycling
recycling factor RRF and EF-G
in eukaryotes, ATPases () help in dissociation of ribosome during recycling
Rli1 (in yeast)
ABCE1 (in humans)
The () is one model of how tRNAs move through the ribosome -> tRNAs ratchet through the interface region, maintaining contact with one subunit while moving with respect to the other
hybrid states model
the hybrid states model suggests that (2)
- tRNAs move first with respect to the large subunit directly following peptide bond formation
- anticodon end of tRNA moves with respect to the small subunit
in the translation cycle, translation factors generally work in 2 ways
- as GTPases
- simply bind to ribosome
many translation factors are (1) that catalyze (2), providing energy and undergoing conformational changes
- GTPases
- GTP hydrolysis
other translation factors simply bind to the ribosome and ()
stop inappropriate interactions with tRNA or other components of translational machinery
() in bacteria prevent initiator tRNA from binding to the A site (thus favoring binding to the P site) and stop the large and small subunits from associating too early
IF1 and IF3
GTPases are related and have a () that interacts with the phosphates on GTP
P-loop motif (Gly-X-X-X-X-Gly-Lys)
GTP hydrolysis and the exchange of GDP for GTP can be promoted with the help of proteins:
- GTPase-activating proteins (GAPs)
- guanine-nucleotide exchange factors (GEFs)
The ribosome itself can act as a ()
GAP
Once a cognate aminoacyl-tRNA is in the A site, the ribosome promotes hydrolysis of GTP by (1), thus promoting full acceptance of the aminoacyl-tRNA into A site and release of (2)
- EFTu
- EFTu-GDP
Translation can proceed without translation factors, but it is (1)–factors contribute to (2) of the reaction
- extremely slow
- speed and accuracy
Many translation factors mimic ()
tRNA structures
mimicking tRNA structure may be the most efficient way for translation factors to ()
access important ribosome interface
aside from translation factors, () also mimic tRNA
class 1 release factors
EFG binds in the A site and promotes translocation of the mRNA-tRNA complex -> very similar in structure to ()
EFTu-tRNA
freeing of initiation codon allows further rounds of initiation to occur -> many ribosomes pile up on mRNA, resulting in structures called ()
polysomes
initiator codon is usually AUG, decoded by ()
initator tRNA
main difference between initiator tRNA in euks vs bacteria
bacterial tRNA has a formyl group on Met
identity element of bacterial initiator tRNA
C-A wobble in acceptor stem
identity element of eukaryotic initiator tRNA
A-U pair in acceptor stem
Both bacterial and eukaryotic initiator tRNA have () in the anticodon stem
three G-C pairs
identity elements of initiator tRNAs are important () so that initiator tRNAs are not loaded into A
anti-determinants for binding of initiator tRNA to EF-Tu
Different GTPases are involved in binding of methionyl-tRNA to the P site in eukaryotes and bacteria:
- Eukaryotes: (1)
- Bacteria: (2)
- eIF2
- IF2
Bacterial mRNAs are often () –having several open reading frame; each open reading frame has its own start and stop codon
polycistronic
Bacterial Initiation codons usually have a () –this is a polypurine tract 6-8 bases upstream of the initiator AUG
Shine-Dalgarno sequence (or ribosome-binding site)
Shine-Dalgarno pairs with a polypyrimidine region in the 3′ end of the bacterial 16S rRNA called the (); this pairing guides initiator AUG into the ribosomal P site
anti-Shine-Dalgarno sequence
The Shine-Dalgarno sequence has the consensus ().
AGGAGGU
sequence deviation from Shine-Dalgarno consensus controls () of translation
strength (how strongly ribosomes bind to mRNA)
In the absence of mRNA or f-Met-tRNAMet, () bind in the A and E sites in the small ribosomal subunit
IF1 and IF3
3 initiation factors that help guide f-Met-tRNAMet to the P site
IF1, IF2, IF3
initiation factor that is a GTPase and is involved in hydrolyzing GTP to provide energy for joining the large and small ribosomal subunits
IF2
All three initiation factors are () when the subunits combine– initiation is complete
displaced
eukaryotic initiation uses () mechanism for identifying AUG start site
scanning
Eukaryotic mRNAs only usually encode one protein–they are ()
monocistronic
in eukaryotes, recognition of the AUG is sensitive to the sequence context–the () (consensus: (A/G)XXAUGG)
Kozak sequence
in eukaryotic mRNA, the 5’ cap is bound by (1) and the 3’ tail by (2). These interact with each other via a complex of other factors
- eIF4E
- PABP
interactions of initiation factors bound to 5’ cap and 3’ tail and other factors form a (), and may function as a quality control to weed out unfinished or damaged mRNAs.
closed loop complex
The (1) ribosomal subunit, bound to a number of initiation factors, is primed to scan the mRNA -> this is called the (2)
- 40S
- “43S” complex, or pre-initiation complex (PIC)
() are orthologs of bacterial IF1 and IF3 and bind in the A and E sites
eIF1A and eIF1
(): initiator tRNA + eIF2 + GTP; important for loading of P site
eIF2 ternary complex
eIF2 ternary complex is brought to () via interactions with eIF3 and eIF4G
closed mRNA loop
() in eukaryotes are thought to unwind mRNA secondary structure and let the initiator tRNA check codons for a suitable AUG
eIF4A and eIF4B
The eukaryotic IF2 (eIF5B) catalyzes () and triggers the dissociation of remaining bound initiation factors.
large subunit joining
summary of decoding step in elongation (for both euks and bacteria)
ribosome selects an aminoacyl-tRNA with an anti-codon that is complementary to the mRNA codon in the A site.
The codon/anti-codon interaction can be cognate: (1), near-cognate: (2) and non-cognate: (3)
- fully accurate
- single mismatch
- more than one mismatch
The fidelity of decoding can be increased (regulated) by two different mechanisms:
- thermodynamic contributions to fidelity
- kinetic contributions to fidelity
Cognate aminoacyl-tRNAs bind more strongly with the ribosome than non-cognate and near-cognate ones
thermodynamic contributions to fidelity
Binding differences between cognate, near-cognate, and non-cognate codons can be utilized both () -> provides the ribosome with two opportunities to discriminate btw cognate and others, thereby increasing fidelity of selection.
before and after GTP hydrolysis on EFTu
in the context of kinetic contributions to decoding fidelity, geometry of the small helix of RNA formed by codon+anticodon is evaluated in its minor groove by () of the ribosome
‘decoding center’
(): conformational changes in the ribosomes triggered by cognate helix recognition leads ribosome to act as GAP on EFTu to increase rate of GTPase activation
kinetic contributions to the fidelity of decoding
increased rate of GTPase activation promotes more rapid () of the aminoacyl-tRNA fully in the A site
accommodation
() starts with the transfer of the polypeptide chain to the aminoacyl-tRNA in the A site
peptide bond formation
the () site has highly conserved rRNA elements that surround 2 tRNA substrates and position them for catalysis
peptidyl transferase active site
nearly no () exist around the peptidyl transferase active site
ribosomal proteins
how is catalysis promoted in the peptidyl transferase active site?
- nucleophilic attack (chemical rxn)
- conformational change due to binding of aminoacyl-tRNA in A site
(1) are universally conserved (2) residues in characteristic loops (3) of 23S rRNA (or 28S rRNA in euk.) form Watson-Crick base pairs with 3’ CCA tails.
- positioning elements
- guanosine
- A and P loops
The () of the peptidyl-tRNA, critically positioned in the active site, catalyzes the transfer by facilitating proton transfer to promote nucleophilic attack
2′ OH
() rearrangements are involved in translocation.
Large structural
EFG can bind in the A site and seems to promote the () -> EFG mimics the tRNA bound to EFTu
structural rearrangements
example of large structural rearrangements involved in translocation
hybrid states (ratchet model)
(), not tRNAs, mediate termination
Class 1 release factors (RF)
main difference between Class 1 RFs and tRNA
RF1s are proteins
Class I RFs in bacteria and eukaryotes are unrelated (i.e. evolutionarily distinct), but have the same () that is needed for catalysis (a, b)
GGQ motif
RF3 (bacteria) derives from (1), while eRF3 (euks.) derives from (2)
- EFG
- EFTu
in bacteria, GTP-bound RF3 promotes () after peptide release, coupling GTP hydrolysis to this event
dissociation of class I RFs (RF1/2)
role of class II eRF3 in euks
- escorts eRF1 to ribosome
- uses GTP hydrolysis to promote its own departure from pre-termination complex
after departure if eRF3, () binds to where eRF3 was to promote peptide release in the absence of ATP hydrolysis
AAA+ ATPase ABCE1
Similar to peptide bond formation, () appears to be a key component in the peptide-releasing hydrolytic reaction, working together with conserved GGQ motif on class 1 release factor.
2’ OH of the peptidyl-tRNA
term for mistakes during translation
miscoding
mismatch in codon/anti-codon helix at triggers a () in the A site
decrease in fidelity
The faulty peptide is detected, and then degraded, likely by the (). This acts as a quality control mechanism
cellular peptidases and proteases
in bacterial ribosome recycling, the recycling substrates are (3)
- ribosome complex
- mRNA
- deacetylated tRNA
in bacterial ribosome recycling, the () acts with EFG (and GTP hydrolysis) and promotes disassembly.
ribosome recycling factor (RRF)
in bacterial ribosome recycling, () binds to the small ribosomal subunit to stabilize the dissociated state
IF3
in eukaryotic ribosomal recycling, eRF1 remains ribosome-bound after the peptide release in the A site in order to ()
promote ribosomal subunit dissociation from the A site
eRF1-promoted subunit dissociation is further enhanced by () through ATP hydrolysis.
AAA+ ATPase ABCE1 in mammals (Rli1in yeast)
Similar to bacteria, () in eukaryotes trap dissociated subunits
core IFs (eIF1, eIF1A, eIF3)
because most bacterial mRNAs are often polycistronic, initiation, elongation, termination, and ribosome take place ()
independently
in bacteria, he rate of () from mRNA is a crucial factor in determining how much ‘scanning’ for another AUG can occur.
small subunit dissociation
for the case of monocistronic eukaryotic mRNA, () often regulate gene expression
upstream open reading frames (uORFs)
upstream open reading frames (uORFs) regulate gene expression via reinitiation of translation from ()
a not fully recycled ribosome
how are ribosomes rescued from ribosome pausing/stalling/arresting?
- arrest-causing mRNA targeted for mRNA decay
- falsely incomplete polypeptide is targeted for proteolysis
- ribosomes are recycled
why are truncated mRNAs problematic in bacteria
bacterial translation can’t distinguish between truncated mRNAs and intact full length mRNAs
measures in eukaryotes that make truncated mRNA less problematic
- cap/tail-dependent translation initiation
- spatially regulated transcription and translation
Bacterial ribosomes arrested by truncated mRNA can be rescued by the ()
tmRNA-SmpB complex
tmRNA first acts as a tRNA: carries () residue to the growing peptide chain
alanine
tmRNA then acts as an mRNA: encodes a short degradation tag of ()
11 a.a. including a stop codon
tagged incomplete polypeptide is targeted to (1) and truncated mRNA is decayed by (2).
- proteases
- RNases
tRNA-SmpB binding is blocked when () in the A site and mRNA channel
mRNA is present
() binds like the C-terminal tail of SmpB and recruits RF2 for termination
ArfA
() binds like termination factors RF1and RF2 and directly releases the polypeptide
ArfB
ArfA production is tightly regulated by (), and is thought to act as a back-up system
tmRNA presence
No-go decay (NGD) rescues ribosome stalling caused by (2)
1) scarce aa-tRNA
2) specific peptide stalling sequences
Non-stop decay (NSD) rescues ribosome arrest caused by (2)
1) premature polyadenylation
2) no stop codon at the end of ORF
long string of As in an ORF without a stop codon
premature polyadenylation
when there is no () at the end of ORF, the ribosome reads into polyA tail
stop codon
In NSD/NGD, () stack up, triggering endonuclease cleavage of mRNA in the A site
stalled ribosomes
Stalled ribosomes can be dissociated through the activity of ()
Pelota and Hbs1
Pelota (Dom34 in yeast) and Hbs1 are () that recruit the recycling factor ABCE1.
termination factor homologs (eRF1 and
eRF3, respectively)
Nonsense-mediated decay (NMD) rescues ribosome arrest caused by ()
premature termination codon (PTC)
In more complex eukaryotes, stop codons are usually found in the (1), so stop codons found elsewhere are marked as (2)
- final exon
- premature
Splicing leaves a protein complex - the EJC - at the ()
exon:exon junction
Stop codons occurring (upstream/downstream) of an EJC indicate that the mRNA is faulty
upstream
The () system targets incomplete proteins for degradation
ribosome quality control (RQC)
in the RQC system, () bind to the 60S subunit with the incomplete protein
NEMF and Ltn1
NEMF and Ltn1 binding to the 60S subunit with the incomplete protein stimulates addition of ()
CAT tails (a string of alanines and threonines)
The CAT tails facilitate (), which leads to degradation of the incomplete protein
ubiquitination
() is where the readout is reprogrammed in an mRNA-specific fashion
Recoding
in recoding, a codon is interpreted differently in a specific (), and in competition
with the normal reading of the codon.
mRNA
() is where stop codons are misread and termination fails to occur.
Nonsense suppression
() is where the mRNA shifts so that peptide synthesis proceeds in a different reading frame.
Frameshifting
Nonsense suppression is rare, but more common when associated with ()
specific mRNA elements
A hexanucleotide motif () found 3′ of the stop codon in some viral mRNAs triggers increased read-through by near-cognate aminoacyl-tRNAs.
CARYYA; R for purines, Y for pyrimidines
() in Murine Leukemia Virus (MuLV) is made by nonsense suppression.
Gag-Pol precursor
Sometimes, UAG is misread by Gln-tRNAGln promoted by a 3′ proximal () in the mRNA (though it still needs to compete with termination factors) -> producing Gag-Pol fusion gene.
pseudoknot
Stop codons can also allow incorporation of ()
non-standard amino acids.
(1)– the “twenty-first amino acid”-is similar to cysteine, but has a (2) instead of a sulfur.
- Selenocysteine
2 selenium
Selenocysteine is incorporated into several enzymes in catalytic sites, where it can act as a ().
strong reducing agent
In E.coli, the () is found immediately 3′ of the UGA that will be recoded
SelenoCysteine Insertion Sequence (SECIS)
A twenty-second amino acid () is a modified lysine found in methyltransferase genes at catalytic sites
pyrrolysine
Pyrrolysine is incorporated at the () in a similar way to selenocysteine.
UGA stop codon
EFTu-a standard pathway-is thought to be involved in loading of the ().
special tRNA
If the ribosome moves by a different number of nucleotides (a number that is not a multiple of three), the reading frame is ().
shifted
Frameshifting occurs most often () nucleotides from the original, in very specific mRNA contexts.
+1 or -1
() frameshifting can be involved in gene regulation
Programmed
An example of programmed frameshifting is the production of ()
bacterial termination factor RF2
Frameshifting is also needed in many retroviruses for the production of ()
Pol
() are small molecules that kill or disrupt organism growth.
Antibiotics
() mean that some good antibiotics are those that target the ribosome and other translation proteins.
Small differences in translation between bacteria and eukaryotes
stops bacterial growth by blocking the synthesis of peptidoglycans required for cell wall.
penicillin
(): selectively inhibits bacterial transcription by targeting distinctive pockets on bacterial RNA Pol.
Rifampicin
Two important naturally-occurring antibiotic groups are the (1) and the (2)
- aminoglycosides (including kanamycin)
- macrolides (including erythromycin
() and similar drugs block the tunnel in the ribosome that the peptide exits from. This stops translation by preventing it from proceeding.
Erythromycin
Bacteria can develop () to antibiotics that interfere with translation
resistance
Mutations that confer resistance are often found in parts of the (). The location and activity of the mutations can tell us more about how ribosomes work.
ribosome
() acts as a miscoding agent–causing ribosomes to misread mRNA so proteins are full of errors.
streptomycin
Streptomycin works by binding the small ribosomal subunit and induces conformational changes that normally only occur when () – thus allowing incorrect amino acids to be incorporated.
the cognate tRNA binds
Streptomycin-resistant bacteria have mutations near the streptomycin binding pocket–these mutations cause translation to slow down and increase fidelity. (())
restrictive protein synthesis
Organisms often produce antibiotics to (1) or as a (2).
- reduce local competition
- defense mechanism
A new synthetic class–()–is structurally different from natural antibiotics, so resistance has been slow to develop.
oxazolidinones
example of oxazolidinones
linezolid
