Dual binding mode of the nascent polypeptide-associated complex reveals a novel universal adapter site on the ribosome.
Nascent polypeptide-associated complex (NAC) was identified in eukaryotes as the first cytosolic factor that contacts the nascent polypeptide chain emerging from the ribosome. NAC is present as a homodimer in archaea and as a highly conserved heterodimer in eukaryotes. Mutations in NAC cause severe embryonically lethal phenotypes in mice, Drosophila melanogaster, and Caenorhabditis elegans. In the yeast Saccharomyces cerevisiae NAC is quantitatively associated with ribosomes. Here we show that NAC contacts several ribosomal proteins. The N terminus of betaNAC, however, specifically contacts near the tunnel exit ribosomal protein Rpl31, which is unique to eukaryotes and archaea. Moreover, the first 23 amino acids of betaNAC are sufficient to direct an otherwise non-associated protein to the ribosome. In contrast, alphaNAC (Egd2p) contacts Rpl17, the direct neighbor of Rpl31 at the ribosomal tunnel exit site. Rpl31 was also recently identified as a contact site for the SRP receptor and the ribosome-associated complex. Furthermore, in Escherichia coli peptide deformylase (PDF) interacts with the corresponding surface area on the eubacterial ribosome. In addition to the previously identified universal adapter site represented by Rpl25/Rpl35, we therefore refer to Rpl31/Rpl17 as a novel universal docking site for ribosome-associated factors on the eukaryotic ribosome.
Pech
Markus
M
Department of Biochemistry, Ludwig-Maximilians-Universität München, Gene Center Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Spreter
Thomas
T
Beckmann
Roland
R
Beatrix
Birgitta
B
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D018833:Chaperonins / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D010455:Peptides / Q000737:chemistry*; D010641:Phenotype; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry*
D000596:Amino Acids; D003432:Cross-Linking Reagents; D010455:Peptides; D012269:Ribosomal Proteins; C032493:ribosomal protein L17; C041672:ribosomal protein L34; D018833:Chaperonins
Nat Struct Mol Biol. 2010 Mar;17(3):313-7
20139981
J Biol Chem. 2006 Feb 3;281(5):2847-57
16316984
J Investig Med. 2002 Jul;50(4):293-301
12109594
FEBS Lett. 2000 Jun 30;476(1-2):22-6
10878243
J Cell Sci. 2001 Jul;114(Pt 14):2641-8
11683391
J Biol Chem. 2005 Apr 22;280(16):15849-54
15665334
Science. 2006 May 5;312(5774):745-7
16675701
Science. 2009 Dec 4;326(5958):1369-73
19933108
Biochemistry. 1994 May 17;33(19):5661-73
8180191
J Mol Biol. 1993 Jul 20;232(2):584-99
8345525
Transgenic Res. 1995 Jul;4(4):264-9
7655515
Genome Biol. 2006;7(3):208
16584537
Cell. 2001 Nov 2;107(3):361-72
11701126
Nature. 2004 Feb 26;427(6977):808-14
14985753
Nature. 2008 Mar 6;452(7183):108-11
18288106
Nat Struct Mol Biol. 2005 Nov;12(11):1015-6
16244660
J Biol Chem. 2000 Dec 1;275(48):37838-45
10982809
Nature. 2002 Sep 12;419(6903):171-4
12226666
Mol Cell. 2009 May 15;34(3):344-53
19450532
Genome Res. 1999 Jul;9(7):608-28
10413400
Cell. 2001 Nov 30;107(5):679-88
11733066
Yeast. 1999 Mar 30;15(5):397-407
10219998
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13425-30
9811816
Cold Spring Harb Symp Quant Biol. 1995;60:47-56
8824377
Mol Cell Biol. 1998 Mar;18(3):1303-11
9488445
Nucleic Acids Res. 2002 Dec 15;30(24):5382-90
12490706
Cancer Lett. 2000 Aug 11;156(2):191-8
10880769
Nature. 2003 Aug 28;424(6952):1066-71
12944970
PLoS One. 2009;4(3):e5055
19330035
J Cell Biol. 1995 Aug;130(3):519-28
7622554
Mol Biol Cell. 2008 Dec;19(12):5279-88
18829863
Science. 2000 Aug 11;289(5481):905-20
10937989
Development. 2000 Feb;127(3):559-72
10631177
J Biol Chem. 2007 Oct 5;282(40):29222-9
17666392
Mol Biol Cell. 1999 Oct;10(10):3289-99
10512867
Nature. 1994 Aug 11;370(6489):434-40
8047162
Cell Death Differ. 2009 Nov;16(11):1505-14
19609276
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5411-5
7777521
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5452-7
10318904
Nat Struct Mol Biol. 2009 Jun;16(6):589-97
19491936
AIDS. 1998 Apr 16;12(6):563-70
9583595
Genes Dev. 1996 Jul 15;10(14):1763-72
8698236
FEBS Lett. 2002 Apr 10;516(1-3):213-6
11959135
Nat Struct Mol Biol. 2009 Jun;16(6):574-81
19491934
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9435-9
7568149
J Biol Chem. 2007 Mar 16;282(11):7809-16
17229726
Proc Natl Acad Sci U S A. 1984 Aug;81(15):4819-23
6235522