翻译（第二讲）2.pptVIP

New Interaction Between Old Partners Delivery of fMet-tRNA via eIF2 More on eIF2 eIF2 is a 127 kDa trimeric complex highly conserved in eukaryotes eIF2a (36 kDa) has a crucial phosphorylation site at S51 eIF2? (39 kDa) function not clear eIF2? (52 kDa) GTP-binding There is no structure yet of entire eIF2 N-terminus of eIF2a has OB fold crystal structure of N-terminal half has been solved (Jon Clardy lab, JBC 277, 17057 (2002) Ser51 sits on a flexible loop Ser 51 phosphorylation leads to a conformational change that causes formation of a tight complex with eIF2B and initiation is inhibited eIF2 consists of three subunits Significance of Ser 51 phosphorylation Ser51 is phosphorylated by kinases, such as double-stranded RNA-activted protein kinase PKR PERK = PKR-like ER kinase Heme-regulatd eIF2a kinase (HRI = heme-regulated inhibvitor) GCN2 in yeast Reversible phosphorylation provides the cells with a mechanism to regulate the the amount of mRNA rapidly and reversibly in response to a variety of stimuli PKR: response to double-stranded RNA virus PKR-induced eIF2a phosphorylation can cause apoptosis Iron deficiency - heme deficiency activates HRI -Ser51 phosphorylation and downregulation of translation in erythrocytes PERK regulates translation in the ER in response to stress Recruitment of mRNA to the 43S ribosomal subunit Recruitment of mRNA to the 43S ribosomal subunit Regulation of translation initiation by 4E-BP eIF4E binding to eIF4G is inhibited by 4E-BP eIF4G and 4E-BP share a consensus binding sequence YxxxxLF Growth factors or hormones may cause hyperphosphorylation of 4EBP , dissociation and formation of preinitiation complex Translation initiated Hierarchical phosphorylation of 4E-BP Initiation via Internal Ribosome Entry Sites Eukaryotic Translation Initiation - Summary Eukaryotic Translation Initiation - details Eukaryotic Translation Initiation - Details eIF1A (IF1 homolog) has OB fold plus an additional domain and long flexible tails eIF1A b