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De novo protein PDB id
1na3
Jmol
Contents
Protein chains
86 a.a. *
Ligands
TRS
IPT ×2
Metals
_MG ×2
Waters ×90
* Residue conservation analysis
PDB id:
1na3
Name: De novo protein
Title: Design of stable alpha-helical arrays from an idealized tpr motif
Structure: Designed protein ctpr2. Chain: a, b. Engineered: yes
Source: Unidentified. Organism_taxid: 32644. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.55Å     R-factor:   0.181     R-free:   0.207
Authors: E.Main,Y.Xiong,M.Cocco,L.D'Andrea,L.Regan
Key ref:
E.R.Main et al. (2003). Design of stable alpha-helical arrays from an idealized TPR motif. Structure, 11, 497-508. PubMed id: 12737816 DOI: 10.1016/S0969-2126(03)00076-5
Date:
26-Nov-02     Release date:   03-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

 

 
DOI no: 10.1016/S0969-2126(03)00076-5 Structure 11:497-508 (2003)
PubMed id: 12737816  
 
 
Design of stable alpha-helical arrays from an idealized TPR motif.
E.R.Main, Y.Xiong, M.J.Cocco, L.D'Andrea, L.Regan.
 
  ABSTRACT  
 
The tetratricopeptide repeat (TPR) is a 34-amino acid alpha-helical motif that occurs in over 300 different proteins. In the different proteins, three to sixteen or more TPR motifs occur in tandem arrays and function to mediate protein-protein interactions. The binding specificity of each TPR protein is different, although the underlying structural motif is the same. Here we describe a statistical approach to the design of an idealized TPR motif. We present the high-resolution X-ray crystal structures (to 1.55 and 1.6 A) of designed TPR proteins and describe their solution properties and stability. A detailed analysis of these structures provides an understanding of the TPR motif, how it is repeated to give helical arrays with different superhelical twists, and how a very stable framework may be constructed for future functional designs.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Structural Features of CTPR2/3(A) Representation of the electron density of CTPR2 in the vicinity of Tyr23(B2) and Tyr24(B2). A 2F[o] - F[c] map (blue), contoured at 1 s, is displayed over a stick model of the structure to demonstrate the quality of the data.(B-D) Representation of the overall folds of (B) CTPR2 and (C) CTPR3 and (D) a stereo view of the overlaid structures of CTPR2 (red) and CTPR3 (blue). They are represented by a tubular worm that snakes through their C^a backbones. CTPR2 (red) corresponds to 86 amino acids from Gly3 to Gly15(solvating helix), and CTPR3 (blue) corresponds to 119 amino acids from Asn2 to Gly15(solvating helix). The N and C termini are marked on each diagram.(E) An illustration showing the two IPTG molecules (space fill, purple and blue) that induce a dimer interface between two molecules of CTPR3 (rendered as a cyan and red C^a trace). The side chains of residues that interact with the IPTG are rendered as sticks, with the chloride ion caught between the two IPTG molecules rendered as green space fills. (A)-(E) were produced with SPOCK [53].
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 497-508) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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The contribution of entropy, enthalpy, and hydrophobic desolvation to cooperativity in repeat-protein folding.
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PDB code: 2l6b
21346797 V.Parashar, N.Mirouze, D.A.Dubnau, and M.B.Neiditch (2011).
Structural basis of response regulator dephosphorylation by rap phosphatases.
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PDB code: 3q15
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Crystal structure of a designed tetratricopeptide repeat module in complex with its peptide ligand.
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PDB code: 3kd7
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A generalized approach to sampling backbone conformations with RosettaDock for CAPRI rounds 13-19.
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20065032 A.Vural, S.Oner, N.An, V.Simon, D.Ma, J.B.Blumer, and S.M.Lanier (2010).
Distribution of activator of G-protein signaling 3 within the aggresomal pathway: role of specific residues in the tetratricopeptide repeat domain and differential regulation by the AGS3 binding partners Gi(alpha) and mammalian inscuteable.
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20589643 J.Janin (2010).
The targets of CAPRI Rounds 13-19.
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CAPRI targets T29-T42: proving ground for new docking procedures.
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20545845 O.Danot (2010).
The inducer maltotriose binds in the central cavity of the tetratricopeptide-like sensor domain of MalT, a bacterial STAND transcription factor.
  Mol Microbiol, 77, 628-641.  
20220147 S.D'Arcy, O.R.Davies, T.L.Blundell, and V.M.Bolanos-Garcia (2010).
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  J Biol Chem, 285, 14764-14776.
PDB code: 2wvi
20862721 S.Eisenbeis, and B.Höcker (2010).
Evolutionary mechanism as a template for protein engineering.
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20715290 S.Fiorucci, and M.Zacharias (2010).
Binding site prediction and improved scoring during flexible protein-protein docking with ATTRACT.
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20718048 S.J.de Vries, A.S.Melquiond, P.L.Kastritis, E.Karaca, A.Bordogna, M.van Dijk, J.P.Rodrigues, and A.M.Bonvin (2010).
Strengths and weaknesses of data-driven docking in critical assessment of prediction of interactions.
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20589642 S.Qin, and H.X.Zhou (2010).
Selection of near-native poses in CAPRI rounds 13-19.
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20635420 S.Y.Huang, and X.Zou (2010).
MDockPP: A hierarchical approach for protein-protein docking and its application to CAPRI rounds 15-19.
  Proteins, 78, 3096-3103.  
18636480 C.Negron, C.Fufezan, and R.L.Koder (2009).
Geometric constraints for porphyrin binding in helical protein binding sites.
  Proteins, 74, 400-416.  
19515729 E.A.Champion, L.Kundrat, L.Regan, and S.J.Baserga (2009).
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High-resolution NMR characterization of a spider-silk mimetic composed of 15 tandem repeats and a CRGD motif.
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18987995 J.Hernández Torres, N.Papandreou, and J.Chomilier (2009).
Sequence analyses reveal that a TPR-DP module, surrounded by recombinable flanking introns, could be at the origin of eukaryotic Hop and Hip TPR-DP domains and prokaryotic GerD proteins.
  Cell Stress Chaperones, 14, 281-289.  
19362536 M.E.Matyskiela, and D.O.Morgan (2009).
Analysis of activator-binding sites on the APC/C supports a cooperative substrate-binding mechanism.
  Mol Cell, 34, 68-80.  
19198901 O.Mirus, T.Bionda, A.von Haeseler, and E.Schleiff (2009).
Evolutionarily evolved discriminators in the 3-TPR domain of the Toc64 family involved in protein translocation at the outer membrane of chloroplasts and mitochondria.
  J Mol Model, 15, 971-982.  
19289204 T.Aksel, and D.Barrick (2009).
Analysis of repeat-protein folding using nearest-neighbor statistical mechanical models.
  Methods Enzymol, 455, 95.  
19141287 V.M.Bolanos-Garcia, T.Kiyomitsu, S.D'Arcy, D.Y.Chirgadze, J.G.Grossmann, D.Matak-Vinkovic, A.R.Venkitaraman, M.Yanagida, C.V.Robinson, and T.L.Blundell (2009).
The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores.
  Structure, 17, 105-116.
PDB code: 3esl
19805120 Y.Javadi, and E.R.Main (2009).
Exploring the folding energy landscape of a series of designed consensus tetratricopeptide repeat proteins.
  Proc Natl Acad Sci U S A, 106, 17383-17388.  
18644382 A.L.Cortajarena, G.Lois, E.Sherman, C.S.O'Hern, L.Regan, and G.Haran (2008).
Non-random-coil behavior as a consequence of extensive PPII structure in the denatured state.
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17803240 D.Han, K.Kim, J.Oh, J.Park, and Y.Kim (2008).
TPR domain of NrfG mediates complex formation between heme lyase and formate-dependent nitrite reductase in Escherichia coli O157:H7.
  Proteins, 70, 900-914.
PDB code: 2e2e
18483553 D.U.Ferreiro, A.M.Walczak, E.A.Komives, and P.G.Wolynes (2008).
The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures.
  PLoS Comput Biol, 4, e1000070.  
18725399 E.A.Champion, B.H.Lane, M.E.Jackrel, L.Regan, and S.J.Baserga (2008).
A direct interaction between the Utp6 half-a-tetratricopeptide repeat domain and a specific peptide in Utp21 is essential for efficient pre-rRNA processing.
  Mol Cell Biol, 28, 6547-6556.  
17963718 E.Kloss, N.Courtemanche, and D.Barrick (2008).
Repeat-protein folding: new insights into origins of cooperativity, stability, and topology.
  Arch Biochem Biophys, 469, 83-99.  
18776008 J.Koo, S.Tammam, S.Y.Ku, L.M.Sampaleanu, L.L.Burrows, and P.L.Howell (2008).
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  Proteins, 70, 72-82.  
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The highly repetitive region of the Helicobacter pylori CagY protein comprises tandem arrays of an alpha-helical repeat module.
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Comparison of the backbone dynamics of a natural and a consensus designed 3-TPR domain.
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Type III secretion system translocator has a molten globule conformation both in its free and chaperone-bound forms.
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17067634 K.W.Tripp, and D.Barrick (2007).
Enhancing the stability and folding rate of a repeat protein through the addition of consensus repeats.
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17582171 T.Kajander, A.L.Cortajarena, S.Mochrie, and L.Regan (2007).
Structure and stability of designed TPR protein superhelices: unusual crystal packing and implications for natural TPR proteins.
  Acta Crystallogr D Biol Crystallogr, 63, 800-811.
PDB codes: 2avp 2fo7 2hyz
16522802 A.C.Hausrath, and A.Goriely (2006).
Repeat protein architectures predicted by a continuum representation of fold space.
  Protein Sci, 15, 753-760.  
16461275 A.J.Perry, J.M.Hulett, V.A.Likić, T.Lithgow, and P.R.Gooley (2006).
Convergent evolution of receptors for protein import into mitochondria.
  Curr Biol, 16, 221-229.
PDB code: 1zu2
16641492 A.L.Cortajarena, and L.Regan (2006).
Ligand binding by TPR domains.
  Protein Sci, 15, 1193-1198.  
  19704665 A.L.Schapire, V.Valpuesta, and M.A.Botella (2006).
TPR Proteins in Plant Hormone Signaling.
  Plant Signal Behav, 1, 229-230.  
16493627 H.K.Binz, A.Kohl, A.Plückthun, and M.G.Grütter (2006).
Crystal structure of a consensus-designed ankyrin repeat protein: implications for stability.
  Proteins, 65, 280-284.
PDB code: 2bkg
16531226 M.J.Cliff, R.Harris, D.Barford, J.E.Ladbury, and M.A.Williams (2006).
Conformational diversity in the TPR domain-mediated interaction of protein phosphatase 5 with Hsp90.
  Structure, 14, 415-426.
PDB code: 2bug
16803880 S.R.Bushell, S.P.Bottomley, J.Rossjohn, and T.Beddoe (2006).
Tracking the unfolding pathway of a multirepeat protein via tryptophan scanning: evidence of localized instability in the mitochondrial import receptor Tom70.
  J Biol Chem, 281, 24345-24350.  
15634341 C.G.Wilson, T.Kajander, and L.Regan (2005).
The crystal structure of NlpI. A prokaryotic tetratricopeptide repeat protein with a globular fold.
  FEBS J, 272, 166-179.
PDB code: 1xnf
16211069 H.K.Binz, P.Amstutz, and A.Plückthun (2005).
Engineering novel binding proteins from nonimmunoglobulin domains.
  Nat Biotechnol, 23, 1257-1268.  
15935782 J.Kim, S.Sitaraman, A.Hierro, B.M.Beach, G.Odorizzi, and J.H.Hurley (2005).
Structural basis for endosomal targeting by the Bro1 domain.
  Dev Cell, 8, 937-947.
PDB code: 1zb1
16040755 V.M.Bolanos-Garcia, S.Beaufils, A.Renault, J.G.Grossmann, S.Brewerton, M.Lee, A.Venkitaraman, and T.L.Blundell (2005).
The conserved N-terminal region of the mitotic checkpoint protein BUBR1: a putative TPR motif of high surface activity.
  Biophys J, 89, 2640-2649.  
15456751 M.Pekkala, R.Hieta, U.Bergmann, K.I.Kivirikko, R.K.Wierenga, and J.Myllyharju (2004).
The peptide-substrate-binding domain of collagen prolyl 4-hydroxylases is a tetratricopeptide repeat domain with functional aromatic residues.
  J Biol Chem, 279, 52255-52261.
PDB code: 1tjc
14760739 P.Forrer, H.K.Binz, M.T.Stumpp, and A.Plückthun (2004).
Consensus design of repeat proteins.
  Chembiochem, 5, 183-189.  
15316022 T.Beddoe, S.R.Bushell, M.A.Perugini, T.Lithgow, T.D.Mulhern, S.P.Bottomley, and J.Rossjohn (2004).
A biophysical analysis of the tetratricopeptide repeat-rich mitochondrial import receptor, Tom70, reveals an elongated monomer that is inherently flexible, unstable, and unfolds via a multistate pathway.
  J Biol Chem, 279, 46448-46454.  
12948778 E.R.Main, S.E.Jackson, and L.Regan (2003).
The folding and design of repeat proteins: reaching a consensus.
  Curr Opin Struct Biol, 13, 482-489.  
  12737814 K.W.Tripp, and D.Barrick (2003).
Folding by consensus.
  Structure, 11, 486-487.  
12930823 Y.Liao, I.M.Willis, and R.D.Moir (2003).
The Brf1 and Bdp1 subunits of transcription factor TFIIIB bind to overlapping sites in the tetratricopeptide repeats of Tfc4.
  J Biol Chem, 278, 44467-44474.  
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 code is shown on the right.