PDBsum entry 1na3

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De novo protein PDB id
Protein chains
86 a.a. *
IPT ×2
_MG ×2
Waters ×90
* Residue conservation analysis
PDB id:
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
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
26-Nov-02     Release date:   03-Jun-03    
Go to PROCHECK summary

Protein chains
No UniProt id for this chain
Struc: 86 a.a.
Key:    Secondary structure  CATH domain


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.
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
23334420 Y.M.Abbas, A.Pichlmair, M.W.Górna, G.Superti-Furga, and B.Nagar (2013).
Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins.
  Nature, 494, 60-64.
PDB codes: 4hoq 4hor 4hos 4hot 4hou
21280125 A.L.Cortajarena, and L.Regan (2011).
Calorimetric study of a series of designed repeat proteins: Modular structure and modular folding.
  Protein Sci, 20, 336-340.  
21420858 H.Baabur-Cohen, S.Dayalan, I.Shumacher, R.Cohen-Luria, and G.Ashkenasy (2011).
Artificial leucine rich repeats as new scaffolds for protein design.
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21397186 T.Aksel, A.Majumdar, and D.Barrick (2011).
The contribution of entropy, enthalpy, and hydrophobic desolvation to cooperativity in repeat-protein folding.
  Structure, 19, 349-360.
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.
  PLoS Biol, 9, e1000589.
PDB code: 3q15
20089039 A.L.Cortajarena, J.Wang, and L.Regan (2010).
Crystal structure of a designed tetratricopeptide repeat module in complex with its peptide ligand.
  FEBS J, 277, 1058-1066.
PDB code: 3kd7
20535822 A.Sircar, S.Chaudhury, K.P.Kilambi, M.Berrondo, and J.J.Gray (2010).
A generalized approach to sampling backbone conformations with RosettaDock for CAPRI rounds 13-19.
  Proteins, 78, 3115-3123.  
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.
  Mol Cell Biol, 30, 1528-1540.  
20589643 J.Janin (2010).
The targets of CAPRI Rounds 13-19.
  Proteins, 78, 3067-3072.  
20607697 M.Eisenstein, A.Ben-Shimon, Z.Frankenstein, and N.Kowalsman (2010).
CAPRI targets T29-T42: proving ground for new docking procedures.
  Proteins, 78, 3174-3181.  
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).
Defining the molecular basis of BubR1 kinetochore interactions and APC/C-CDC20 inhibition.
  J Biol Chem, 285, 14764-14776.
PDB code: 2wvi
20862721 S.Eisenbeis, and B.Höcker (2010).
Evolutionary mechanism as a template for protein engineering.
  J Pept Sci, 16, 538-544.  
20715290 S.Fiorucci, and M.Zacharias (2010).
Binding site prediction and improved scoring during flexible protein-protein docking with ATTRACT.
  Proteins, 78, 3131-3139.  
20718048 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.
  Proteins, 78, 3242-3249.  
20589642 S.Qin, and H.X.Zhou (2010).
Selection of near-native poses in CAPRI rounds 13-19.
  Proteins, 78, 3166-3173.  
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).
A structural model for the HAT domain of Utp6 incorporating bioinformatics and genetics.
  Protein Eng Des Sel, 22, 431-439.  
19177364 G.D.McLachlan, J.Slocik, R.Mantz, D.Kaplan, S.Cahill, M.Girvin, and S.Greenbaum (2009).
High-resolution NMR characterization of a spider-silk mimetic composed of 15 tandem repeats and a CRGD motif.
  Protein Sci, 18, 206-216.  
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.
  J Mol Biol, 382, 203-212.  
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).
PilF is an outer membrane lipoprotein required for multimerization and localization of the Pseudomonas aeruginosa Type IV pilus secretin.
  J Bacteriol, 190, 6961-6969.
PDB code: 2ho1
18266909 J.W.Hammond, K.Griffin, G.T.Jih, J.Stuckey, and K.J.Verhey (2008).
Co-operative versus independent transport of different cargoes by Kinesin-1.
  Traffic, 9, 725-741.  
17634984 M.Palaiomylitou, A.Tartas, D.Vlachakis, D.Tzamarias, and M.Vlassi (2008).
Investigating the structural stability of the Tup1-interaction domain of Ssn6: evidence for a conformational change on the complex.
  Proteins, 70, 72-82.  
18632570 N.D.Werbeck, P.J.Rowling, V.R.Chellamuthu, and L.S.Itzhaki (2008).
Shifting transition states in the unfolding of a large ankyrin repeat protein.
  Proc Natl Acad Sci U S A, 105, 9982-9987.  
18295231 R.M.Delahay, G.D.Balkwill, K.A.Bunting, W.Edwards, J.C.Atherton, and M.S.Searle (2008).
The highly repetitive region of the Helicobacter pylori CagY protein comprises tandem arrays of an alpha-helical repeat module.
  J Mol Biol, 377, 956-971.  
18566891 V.A.Jarymowycz, A.L.Cortajarena, L.Regan, and M.J.Stone (2008).
Comparison of the backbone dynamics of a natural and a consensus designed 3-TPR domain.
  J Biomol NMR, 41, 169-178.  
17578515 E.Faudry, V.Job, A.Dessen, I.Attree, and V.Forge (2007).
Type III secretion system translocator has a molten globule conformation both in its free and chaperone-bound forms.
  FEBS J, 274, 3601-3610.  
17067634 K.W.Tripp, and D.Barrick (2007).
Enhancing the stability and folding rate of a repeat protein through the addition of consensus repeats.
  J Mol Biol, 365, 1187-1200.  
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.  
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