{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:00:24Z","timestamp":1781110824976,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1978,2]]},"abstract":"\n Protein synthesis in reticulocytes and their lysates is regulated by heme. In heme deficiency a heme-regulated translational inhibitor (HRI) that blocks initiation of polypeptide chains is activated. HRI is a protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) that specifically phosphorylates the 38,000-dalton subunit of the Met-tRNA\n f<\/jats:sub>\n Met<\/jats:sup>\n binding factor (IF), which forms a ternary complex with Met-tRNA\n f<\/jats:sub>\n Met<\/jats:sup>\n and GTP, a finding that suggests that the inhibition by HRI involves the phosphorylation of IF.\n <\/jats:p>\n \n We have investigated the effect of HRI in the partial reactions of protein chain initiation in which the IF-promoted binding of Met-tRNA\n f<\/jats:sub>\n Met<\/jats:sup>\n to 40S ribosomal subunits is enhanced by another initiation factor [ternary complex dissociation factor (TDF)] and AUG. The results show that HRI at very low concentrations markedly inhibits the binding of Met-tRNA\n f<\/jats:sub>\n Met<\/jats:sup>\n to 40S subunits. The inhibitory effect of HRI requires ATP. Under these conditions HRI phosphorylates only the 38,000-dalton subunit of IF.\n <\/jats:p>\n \n The TDF preparations not only promote the binding of the ternary complex to 40S subunits but also promote the dissociation of the ternary complex in the presence of 5 mM Mg\n 2+<\/jats:sup>\n at 0\u00b0. The preincubation of purified IF alone with low concentrations of HRI and ATP does not significantly affect its capacity to form the ternary complex; however, the TDF-promoted dissociation of the ternary complex is inhibited. The nonhydrolyzable analog adenosine 5\u2032-[\u03b2,\u03b3-imido]triphosphate does not substitute for ATP. These findings suggest that phosphorylation causes a conformational modification in IF, which results in inhibition of the interaction between the ternary complex and TDF that is required for the binding of the ternary complex to 40S subunits.\n <\/jats:p>","DOI":"10.1073\/pnas.75.2.745","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T03:39:12Z","timestamp":1149046752000},"page":"745-749","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":57,"title":["Regulation of protein synthesis in rabbit reticulocyte lysates by the heme-regulated protein kinase: Inhibition of interaction of Met-tRNA\n f<\/sub>\n Met<\/sup>\n binding factor with another initiation factor in formation of Met-tRNA\n f<\/sub>\n Met<\/sup>\n \u00b740S ribosomal subunit complexes"],"prefix":"10.1073","volume":"75","author":[{"given":"R. S.","family":"Ranu","sequence":"first","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. M.","family":"London","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"},{"name":"Harvard\u2014MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Nebraska, Lincoln, Nebraska 68588"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Nebraska, Lincoln, Nebraska 68588"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Nebraska, Lincoln, Nebraska 68588"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Ralston","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Nebraska, Lincoln, Nebraska 68588"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Nebraska, Lincoln, Nebraska 68588"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Nebraska, Lincoln, Nebraska 68588"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1978,2]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.75.2.745","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T10:59:59Z","timestamp":1649847599000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.75.2.745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1978,2]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1978,2]]}},"alternative-id":["10.1073\/pnas.75.2.745"],"URL":"https:\/\/doi.org\/10.1073\/pnas.75.2.745","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1978,2]]},"assertion":[{"value":"1978-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}