Met

FIGURE 8.23 Assembly of the Eukaryotic Initiation Complex

A) Assembly of the small subunit plus initiator Met-tRNA involves the binding of factors eIF3 and eIF2.

B) The cap binding protein of eIF4 attaches to the mRNA before it joins the small subunit. C) The mRNA binds to the small subunit via cap binding protein and the 40S initiation complex is assembled. D) Assembly of the large subunit requires factor eIF5. After assembly, eIF2 and eIF3 depart.

mRNA

FIGURE 8.24 Bacterial Ribosomes on Standby During Bad Conditions

Active bacterial ribosomes can become inactive when the RMF protein binds to them. The ribosomes form dimers with the 30S subunits attached to one another. When conditions are favorable, dissociation occurs.

FIGURE 8.24 Bacterial Ribosomes on Standby During Bad Conditions

Active bacterial ribosomes can become inactive when the RMF protein binds to them. The ribosomes form dimers with the 30S subunits attached to one another. When conditions are favorable, dissociation occurs.

^RMF

Active ribosomes

^RMF

Inactive ribosomes the order of assembly of the initiation complex is different. Factor eIF2 binds to the initiator Met-tRNA, factor eIF3 binds to the small (40S) subunit of the ribosome and factor eIF4 binds to the mRNA (via Cap binding protein). These components then assemble to form the initiation complex (Fig. 8.23).

The 40S subunit then moves along the mRNA, starting from the 5'-end, until it finds a start codon. This process is referred to as scanning. Normally the first AUG to be found is used as the start codon, although the sequence surrounding the AUG is important. The consensus is GCCRCCAUGG (R = A or G). If its surrounding sequence is too far from consensus an AUG may be skipped. Once a suitable AUG has been located, eIF5 is needed to allow the 60S subunit to join and for eIF2 and eIF3 to depart.

Protein Synthesis Is Halted When Resources Are Scarce

Proteins make up about two-thirds of the organic matter in a cell and their synthesis consumes a major part of the cell's energy and raw materials. Clearly, when cells run low on nutrients or energy they cannot continue to synthesize proteins at the normal rate. In bacteria, ribosomes are taken out of service during stationary phase or periods of slow growth. A small basic protein, ribosome modulation factor (RMF) binds to ribosomes and inactivates them (Fig. 8.24). The inactive ribosomes exist as dimers. When favorable conditions return, the inactive dimers are disassembled and the ribo-somes are reactivated.

Higher organisms also stop protein synthesis when nutrients or energy run low. However, they do so by inactivating the initiation factors rather than the ribosomes (Fig. 8.25). Initiation factor eIF2 uses energy by hydrolyzing GTP to GDP. After initiation is over, it is released from the ribosome with the GDP still bound. It then binds to eIF2B, which exchanges GDP for GTP, so recycling the eIF2. In times of stress, a kinase phosphorylates eIF2 and prevents the removal of GDP. The GDP bound form of eIF2 cannot initiate translation and protein synthesis is halted.

Exported proteins have a signal sequence at the front.

A Signal Sequence Marks a Protein for Export from the Cell

Once a protein has been made, it must find its correct location. Although cytoplasmic proteins are made in the cell compartment where they belong, other proteins, which do not reside in the cytoplasm, must be transported. Proteins destined to be exported ribosome modulation factor (RMF) Protein that inactivates surplus ribosomes during slow growth or stationary phase in bacteria

When eukaryotes down-regulate the level of protein synthesis, a protein kinase phosphorylates eIF2/GDP. This prevents eIF2B from removing the GDP and eIF2/GDP stays locked in an inactive complex with eIF2B. Absence of active eIF2 decreases the rate of initiation

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