Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome.
Elongation factor P (EF-P) is an essential protein that stimulates the formation of the first peptide bond in protein synthesis. Here we report the crystal structure of EF-P bound to the Thermus thermophilus 70S ribosome along with the initiator transfer RNA N-formyl-methionyl-tRNA(i) (fMet-tRNA(i)(fMet)) and a short piece of messenger RNA (mRNA) at a resolution of 3.5 angstroms. EF-P binds to a site located between the binding site for the peptidyl tRNA (P site) and the exiting tRNA (E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA. Domain II of EF-P interacts with the ribosomal protein L1, which results in the largest movement of the L1 stalk that has been observed in the absence of ratcheting of the ribosomal subunits. EF-P facilitates the proper positioning of the fMet-tRNA(i)(fMet) for the formation of the first peptide bond during translation initiation.
Blaha
Gregor
G
Department of Molecular Biophysics, Yale University, New Haven, CT 06520, USA.
Stanley
Robin E
RE
Steitz
Thomas A
TA
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010442:Peptide Chain Initiation, Translational; D010445:Peptide Elongation Factors / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012358:RNA, Transfer, Met / Q000737:chemistry / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D054681:Ribosome Subunits, Large, Bacterial / Q000378:metabolism; D054680:Ribosome Subunits, Small, Bacterial / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D016963:Thermus thermophilus / Q000737:chemistry / Q000378:metabolism*
D001426:Bacterial Proteins; D010445:Peptide Elongation Factors; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012358:RNA, Transfer, Met; D012269:Ribosomal Proteins; C089238:fMet-tRNA(fMet); C020746:factor EF-P; C028546:ribosomal protein L1
Eur J Biochem. 1980 Nov;112(2):425-30
7007045
Cell Mol Life Sci. 2009 Feb;66(3):423-36
19011758
J Biol Chem. 1978 May 10;253(9):3070-7
641055
FEBS J. 2008 Feb;275(4):671-81
18201202
Biol Chem. 2000 Jul;381(7):553-9
10987361
Gene. 2004 Apr 14;330:169-76
15087136
Cell. 2003 Jul 11;114(1):123-34
12859903
Trends Biochem Sci. 2007 Sep;32(9):434-41
17764954
Mol Cell. 2008 May 9;30(3):348-59
18471980
Mol Cell. 2007 Mar 9;25(5):751-64
17349960
Biochim Biophys Acta. 1990 Aug 27;1050(1-3):160-2
2119810
Cell. 2004 Aug 20;118(4):465-75
15315759
Nature. 2009 May 7;459(7243):118-21
19424157
Science. 2006 Sep 29;313(5795):1935-42
16959973
Mol Cell Biol. 1991 Jun;11(6):3105-14
1903841
J Biol Chem. 1999 Aug 6;274(32):22143-6
10428776
J Mol Biol. 1987 Dec 5;198(3):383-92
2448483
Cell. 2006 Sep 22;126(6):1065-77
16962654
Proc Natl Acad Sci U S A. 1975 Mar;72(3):844-8
1055382
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):224-8
9419357
Mol Cell. 2005 Nov 11;20(3):427-35
16285924
J Cell Biochem. 2006 Feb 15;97(3):583-98
16215987
J Biol Chem. 1983 Aug 25;258(16):10098-103
6350280
Microbiol Mol Biol Rev. 2002 Sep;66(3):460-85, table of contents
12209000
Nat Struct Mol Biol. 2009 May;16(5):528-33
19363482
Nat Struct Mol Biol. 2008 Sep;15(9):910-5
19172743
J Biol Chem. 1998 Jul 31;273(31):19847-52
9677420
J Biol Chem. 1997 Dec 19;272(51):32254-9
9405429
Nature. 2008 Sep 18;455(7211):416-20
18758445
Nat Biotechnol. 2001 Aug;19(8):751-5
11479568
Amino Acids. 2007 Aug;33(2):351-8
17578650
Proc Natl Acad Sci U S A. 1975 Nov;72(11):4257-60
1105576
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9595-600
15210970
Can J Biochem. 1980 Nov;58(11):1312-4
7011506
Biochimie. 1997;79(1):7-11
9195040
Nat Struct Mol Biol. 2006 Mar;13(3):234-41
16501572
Microbiol Mol Biol Rev. 2005 Mar;69(1):101-23
15755955
Cell. 2005 Jun 3;121(5):703-12
15935757
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2571-6
19190181
Science. 2001 May 4;292(5518):883-96
11283358