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RNA binding protein PDB id
3h3d
Jmol
Contents
Protein chains
313 a.a. *
Waters ×335
* Residue conservation analysis
PDB id:
3h3d
Name: RNA binding protein
Title: Drosophila pumilio RNA binding domain (puf domain)
Structure: Maternal protein pumilio. Chain: x, y. Fragment: puf domain. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: pumilio. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.254     R-free:   0.298
Authors: T.A.Edwards,A.K.Aggarwal,R.P.Wharton
Key ref:
T.A.Edwards et al. (2001). Structure of Pumilio reveals similarity between RNA and peptide binding motifs. Cell, 105, 281-289. PubMed id: 11336677 DOI: 10.1016/S0092-8674(01)00318-X
Date:
16-Apr-09     Release date:   28-Apr-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P25822  (PUM_DROME) -  Maternal protein pumilio
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1533 a.a.
313 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     binding     2 terms  

 

 
DOI no: 10.1016/S0092-8674(01)00318-X Cell 105:281-289 (2001)
PubMed id: 11336677  
 
 
Structure of Pumilio reveals similarity between RNA and peptide binding motifs.
T.A.Edwards, S.E.Pyle, R.P.Wharton, A.K.Aggarwal.
 
  ABSTRACT  
 
Translation regulation plays an essential role in the differentiation and development of animal cells. One well-studied case is the control of hunchback mRNA during early Drosophila embryogenesis by the trans-acting factors Pumilio, Nanos, and Brain Tumor. We report here a crystal structure of the critical region of Pumilio, the Puf domain, that organizes a multivalent repression complex on the 3' untranslated region of hunchback mRNA. The structure reveals an extended, rainbow shaped molecule, with tandem helical repeats that bear unexpected resemblance to the armadillo repeats in beta-catenin and the HEAT repeats in protein phosphatase 2A. Based on the structure and genetic experiments, we identify putative interaction surfaces for hunchback mRNA and the cofactors Nanos and Brain Tumor. This analysis suggests that similar features in helical repeat proteins are used to bind extended peptides and RNA.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Pum Puf Domain Structure
The Puf domain contains eight tandem Puf repeats (shown in different colors) that together comprise a single contiguous domain. Inset is a magnification of a single repeat. Each repeat is composed of three α helices (H1, H2, and H3). 		Figure 6.
Figure 6. A Hypothetical Model of the Pum/NRE/Nos/Brat Repression Complex
The 3′UTR of hb mRNA (NRE) is postulated to bind the inner concave surface of Pum, while the cofactors Nos and Brat are hypothesized to bind the outer convex surface.
 
  The above figures are reprinted by permission from Cell Press: Cell (2001, 105, 281-289) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21358629 J.P.Mackay, J.Font, and D.J.Segal (2011).
The prospects for designer single-stranded RNA-binding proteins.
  Nat Struct Mol Biol, 18, 256-261.  
20609625 S.Kramer, and M.Carrington (2011).
Trans-acting proteins regulating mRNA maturation, stability and translation in trypanosomatids.
  Trends Parasitol, 27, 23-30.  
21115348 T.Quenault, T.Lithgow, and A.Traven (2011).
PUF proteins: repression, activation and mRNA localization.
  Trends Cell Biol, 21, 104-112.  
20705650 A.G.Cridge, L.M.Castelli, J.B.Smirnova, J.N.Selley, W.Rowe, S.J.Hubbard, J.E.McCarthy, M.P.Ashe, C.M.Grant, and G.D.Pavitt (2010).
Identifying eIF4E-binding protein translationally-controlled transcripts reveals links to mRNAs bound by specific PUF proteins.
  Nucleic Acids Res, 38, 8039-8050.  
19790240 B.Ewen-Campen, E.E.Schwager, and C.G.Extavour (2010).
The molecular machinery of germ line specification.
  Mol Reprod Dev, 77, 3.  
20153321 D.Droll, S.Archer, K.Fenn, P.Delhi, K.Matthews, and C.Clayton (2010).
The trypanosome Pumilio-domain protein PUF7 associates with a nuclear cyclophilin and is involved in ribosomal RNA maturation.
  FEBS Lett, 584, 1156-1162.  
20543818 J.E.Braun, F.Tritschler, G.Haas, C.Igreja, V.Truffault, O.Weichenrieder, and E.Izaurralde (2010).
The C-terminal alpha-alpha superhelix of Pat is required for mRNA decapping in metazoa.
  EMBO J, 29, 2368-2380.
PDB codes: 2xeq 2xer 2xes
20214804 P.P.Tam, I.H.Barrette-Ng, D.M.Simon, M.W.Tam, A.L.Ang, and D.G.Muench (2010).
The Puf family of RNA-binding proteins in plants: phylogeny, structural modeling, activity and subcellular localization.
  BMC Plant Biol, 10, 44.  
19274078 A.K.Farina, Y.S.Bong, C.M.Feltes, and S.W.Byers (2009).
Post-transcriptional regulation of cadherin-11 expression by GSK-3 and beta-catenin in prostate and breast cancer cells.
  PLoS ONE, 4, e4797.  
19682068 C.W.Francischini, and R.B.Quaggio (2009).
Molecular characterization of Arabidopsis thaliana PUF proteins--binding specificity and target candidates.
  FEBS J, 276, 5456-5470.  
19918084 D.Zhu, C.R.Stumpf, J.M.Krahn, M.Wickens, and T.M.Hall (2009).
A 5' cytosine binding pocket in Puf3p specifies regulation of mitochondrial mRNAs.
  Proc Natl Acad Sci U S A, 106, 20192-20197.
PDB codes: 3k49 3k4e
19186050 G.Lu, S.J.Dolgner, and T.M.Hall (2009).
Understanding and engineering RNA sequence specificity of PUF proteins.
  Curr Opin Struct Biol, 19, 110-115.  
19319195 M.W.Kuo, S.H.Wang, J.C.Chang, C.H.Chang, L.J.Huang, H.H.Lin, A.L.Yu, W.H.Li, and J.Yu (2009).
A novel puf-A gene predicted from evolutionary analysis is involved in the development of eyes and primordial germ-cells.
  PLoS ONE, 4, e4980.  
19714224 S.K.Archer, V.D.Luu, R.A.de Queiroz, S.Brems, and C.Clayton (2009).
Trypanosoma brucei PUF9 regulates mRNAs for proteins involved in replicative processes over the cell cycle.
  PLoS Pathog, 5, e1000565.  
19372537 Y.K.Gupta, T.H.Lee, T.A.Edwards, C.R.Escalante, L.Y.Kadyrova, R.P.Wharton, and A.K.Aggarwal (2009).
Co-occupancy of two Pumilio molecules on a single hunchback NRE.
  RNA, 15, 1029-1035.  
19901328 Y.Wang, L.Opperman, M.Wickens, and T.M.Hall (2009).
Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein.
  Proc Natl Acad Sci U S A, 106, 20186-20191.
PDB codes: 3k5q 3k5y 3k5z 3k61 3k62 3k64
19369425 Y.Y.Koh, L.Opperman, C.Stumpf, A.Mandan, S.Keles, and M.Wickens (2009).
A single C. elegans PUF protein binds RNA in multiple modes.
  RNA, 15, 1090-1099.  
18223680 A.Bonnomet, M.Polette, K.Strumane, C.Gilles, V.Dalstein, C.Kileztky, G.Berx, F.van Roy, P.Birembaut, and B.Nawrocki-Raby (2008).
The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression.
  Oncogene, 27, 3692-3699.  
18776931 A.Galgano, M.Forrer, L.Jaskiewicz, A.Kanitz, M.Zavolan, and A.P.Gerber (2008).
Comparative analysis of mRNA targets for human PUF-family proteins suggests extensive interaction with the miRNA regulatory system.
  PLoS ONE, 3, e3164.  
18411299 A.R.Morris, N.Mukherjee, and J.D.Keene (2008).
Ribonomic analysis of human Pum1 reveals cis-trans conservation across species despite evolution of diverse mRNA target sets.
  Mol Cell Biol, 28, 4093-4103.  
18579869 C.R.Stumpf, J.Kimble, and M.Wickens (2008).
A Caenorhabditis elegans PUF protein family with distinct RNA binding specificity.
  RNA, 14, 1550-1557.  
18039654 F.Tavares-Carreón, Y.Camacho-Villasana, A.Zamudio-Ochoa, M.Shingú-Vázquez, A.Torres-Larios, and X.Pérez-Martínez (2008).
The pentatricopeptide repeats present in Pet309 are necessary for translation but not for stability of the mitochondrial COX1 mRNA in yeast.
  J Biol Chem, 283, 1472-1479.  
18327269 M.T.Miller, J.J.Higgin, and T.M.Hall (2008).
Basis of altered RNA-binding specificity by PUF proteins revealed by crystal structures of yeast Puf4p.
  Nat Struct Mol Biol, 15, 397-402.
PDB codes: 3bwt 3bx2 3bx3
18094119 R.J.Ulbricht, and W.M.Olivas (2008).
Puf1p acts in combination with other yeast Puf proteins to control mRNA stability.
  RNA, 14, 246-262.  
18328718 Y.K.Gupta, D.T.Nair, R.P.Wharton, and A.K.Aggarwal (2008).
Structures of human Pumilio with noncognate RNAs reveal molecular mechanisms for binding promiscuity.
  Structure, 16, 549-557.
PDB codes: 3bsb 3bsx
17889667 H.H.Lee, Y.S.Kim, K.H.Kim, I.Heo, S.K.Kim, O.Kim, H.K.Kim, J.Y.Yoon, H.S.Kim, d.o. .J.Kim, S.J.Lee, H.J.Yoon, S.J.Kim, B.G.Lee, H.K.Song, V.N.Kim, C.M.Park, and S.W.Suh (2007).
Structural and functional insights into Dom34, a key component of no-go mRNA decay.
  Mol Cell, 27, 938-950.
PDB code: 2qi2
17412319 M.J.Nolde, N.Saka, K.L.Reinert, and F.J.Slack (2007).
The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3'UTR-mediated repression of the let-7 microRNA target gene, hbl-1.
  Dev Biol, 305, 551-563.  
16537387 A.P.Gerber, S.Luschnig, M.A.Krasnow, P.O.Brown, and D.Herschlag (2006).
Genome-wide identification of mRNAs associated with the translational regulator PUMILIO in Drosophila melanogaster.
  Proc Natl Acad Sci U S A, 103, 4487-4492.  
16954190 C.G.Cheong, and T.M.Hall (2006).
Engineering RNA sequence specificity of Pumilio repeats.
  Proc Natl Acad Sci U S A, 103, 13635-13639.  
16809390 S.Archak, and J.Nagaraju (2006).
Eicosapentapeptide repeats (EPRs): novel repeat proteins specific to flowering plants.
  Bioinformatics, 22, 2455-2458.  
15769874 D.Bernstein, B.Hook, A.Hajarnavis, L.Opperman, and M.Wickens (2005).
Binding specificity and mRNA targets of a C. elegans PUF protein, FBF-1.
  RNA, 11, 447-458.  
15806553 J.Urano, M.S.Fox, and R.A.Reijo Pera (2005).
Interaction of the conserved meiotic regulators, BOULE (BOL) and PUMILIO-2 (PUM2).
  Mol Reprod Dev, 71, 290-298.  
16244662 L.Opperman, B.Hook, M.DeFino, D.S.Bernstein, and M.Wickens (2005).
A single spacer nucleotide determines the specificities of two mRNA regulatory proteins.
  Nat Struct Mol Biol, 12, 945-951.  
16244132 S.S.Houshmandi, and W.M.Olivas (2005).
Yeast Puf3 mutants reveal the complexity of Puf-RNA binding and identify a loop required for regulation of mRNA decay.
  RNA, 11, 1655-1666.  
15853794 Y.Chen, and G.Varani (2005).
Protein families and RNA recognition.
  FEBS J, 272, 2088-2097.  
14730349 C.C.Milburn, J.Boudeau, M.Deak, D.R.Alessi, and D.M.van Aalten (2004).
Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor.
  Nat Struct Mol Biol, 11, 193-200.
PDB codes: 1upk 1upl
15337848 J.S.Jackson, S.S.Houshmandi, F.Lopez Leban, and W.M.Olivas (2004).
Recruitment of the Puf3 protein to its mRNA target for regulation of mRNA decay in yeast.
  RNA, 10, 1625-1636.  
12511597 F.L.Moore, J.Jaruzelska, M.S.Fox, J.Urano, M.T.Firpo, P.J.Turek, D.M.Dorfman, and R.A.Pera (2003).
Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-like proteins.
  Proc Natl Acad Sci U S A, 100, 538-543.  
14617068 P.M.Williams, and A.Barkan (2003).
A chloroplast-localized PPR protein required for plastid ribosome accumulation.
  Plant J, 36, 675-686.  
12660986 S.K.Singh, M.M.Babu, and P.Balaram (2003).
Registering alpha-helices and beta-strands using backbone C-H...O interactions.
  Proteins, 51, 167-171.  
14561773 T.A.Edwards, B.D.Wilkinson, R.P.Wharton, and A.K.Aggarwal (2003).
Model of the brain tumor-Pumilio translation repressor complex.
  Genes Dev, 17, 2508-2513.
PDB code: 1q7f
12858164 T.Aviv, Z.Lin, S.Lau, L.M.Rendl, F.Sicheri, and C.A.Smibert (2003).
The RNA-binding SAM domain of Smaug defines a new family of post-transcriptional regulators.
  Nat Struct Biol, 10, 614-621.  
12942139 T.M.Hall (2003).
SAM breaks its stereotype.
  Nat Struct Biol, 10, 677-679.  
12702867 T.Pawson, and P.Nash (2003).
Assembly of cell regulatory systems through protein interaction domains.
  Science, 300, 445-452.  
12045185 A.H.Auchincloss, W.Zerges, K.Perron, J.Girard-Bascou, and J.D.Rochaix (2002).
Characterization of Tbc2, a nucleus-encoded factor specifically required for translation of the chloroplast psbC mRNA in Chlamydomonas reinhardtii.
  J Cell Biol, 157, 953-962.  
  12136020 B.A.Schweers, K.J.Walters, and M.Stern (2002).
The Drosophila melanogaster translational repressor pumilio regulates neuronal excitability.
  Genetics, 161, 1177-1185.  
11992126 C.H.Williams, T.J.Stillman, V.V.Barynin, S.E.Sedelnikova, Y.Tang, J.Green, J.R.Guest, and P.J.Artymiuk (2002).
E. coli aconitase B structure reveals a HEAT-like domain with implications for protein-protein recognition.
  Nat Struct Biol, 9, 447-452.
PDB code: 1l5j
  12414187 K.A.Dean, A.K.Aggarwal, and R.P.Wharton (2002).
Translational repressors in Drosophila.
  Trends Genet, 18, 572-577.  
12409450 L.Cui, Q.Fan, and J.Li (2002).
The malaria parasite Plasmodium falciparum encodes members of the Puf RNA-binding protein family with conserved RNA binding activity.
  Nucleic Acids Res, 30, 4607-4617.  
12455976 M.G.Andersson, and L.Cerenius (2002).
Pumilio homologue from saprolegnia parasitica specifically expressed in undifferentiated spore cysts.
  Eukaryot Cell, 1, 105-111.  
  11858839 M.Wickens, D.S.Bernstein, J.Kimble, and R.Parker (2002).
A PUF family portrait: 3'UTR regulation as a way of life.
  Trends Genet, 18, 150-157.  
11917006 V.Anantharaman, E.V.Koonin, and L.Aravind (2002).
Comparative genomics and evolution of proteins involved in RNA metabolism.
  Nucleic Acids Res, 30, 1427-1464.  
  12202039 X.Wang, J.McLachlan, P.D.Zamore, and T.M.Hall (2002).
Modular recognition of RNA by a human pumilio-homology domain.
  Cell, 110, 501-512.
PDB codes: 1m8w 1m8x 1m8y
11590142 C.Morris-Desbois, S.Réty, M.Ferro, J.Garin, and P.Jalinot (2001).
The human protein HSPC021 interacts with Int-6 and is associated with eukaryotic translation initiation factor 3.
  J Biol Chem, 276, 45988-45995.  
  11516967 E.B.Goodwin (2001).
Translational repression: not just a Puf of smoke.
  Curr Biol, 11, R607-R609.  
  11780640 E.K.White, T.Moore-Jarrett, and H.E.Ruley (2001).
PUM2, a novel murine puf protein, and its consensus RNA-binding site.
  RNA, 7, 1855-1866.  
12762036 M.Wickens, D.Bernstein, S.Crittenden, C.Luitjens, and J.Kimble (2001).
PUF proteins and 3'UTR regulation in the Caenorhabditis elegans germ line.
  Cold Spring Harb Symp Quant Biol, 66, 337-343.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.