PDBsum entry 1wy3

Go to PDB code: 
protein links
Structural protein PDB id
Protein chain
35 a.a. *
Waters ×51
* Residue conservation analysis
PDB id:
Name: Structural protein
Title: Chicken villin subdomain hp-35, k65(nle), n68h, ph7.0
Structure: Villin. Chain: a. Fragment: vhp. Engineered: yes. Mutation: yes
Source: Synthetic: yes. Other_details: synthetic peptide, sequence corresponds to chicken villin residues 792-826, residue 65 is norleucine (lysine without terminal nh3 group)
0.95Å     R-factor:   0.145     R-free:   0.171
Authors: T.K.Chiu,J.Kubelka,R.Herbst-Irmer,W.A.Eaton,J.Hofrichter, D.R.Davies
Key ref:
T.K.Chiu et al. (2005). High-resolution x-ray crystal structures of the villin headpiece subdomain, an ultrafast folding protein. Proc Natl Acad Sci U S A, 102, 7517-7522. PubMed id: 15894611 DOI: 10.1073/pnas.0502495102
04-Feb-05     Release date:   03-May-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P02640  (VILI_CHICK) -  Villin-1
826 a.a.
35 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)


DOI no: 10.1073/pnas.0502495102 Proc Natl Acad Sci U S A 102:7517-7522 (2005)
PubMed id: 15894611  
High-resolution x-ray crystal structures of the villin headpiece subdomain, an ultrafast folding protein.
T.K.Chiu, J.Kubelka, R.Herbst-Irmer, W.A.Eaton, J.Hofrichter, D.R.Davies.
The 35-residue subdomain of the villin headpiece (HP35) is a small ultrafast folding protein that is being intensely studied by experiments, theory, and simulations. We have solved the x-ray structures of HP35 and its fastest folding mutant [K24 norleucine (nL)] to atomic resolution and compared their experimentally measured folding kinetics by using laser temperature jump. The structures, which are in different space groups, are almost identical to each other but differ significantly from previously solved NMR structures. Hence, the differences between the x-ray and NMR structures are probably not caused by lattice contacts or crystal/solution differences, but reflect the higher accuracy of the x-ray structures. The x-ray structures reveal important details of packing of the hydrophobic core and some additional features, such as cross-helical H bonds. Comparison of the x-ray structures indicates that the nL substitution produces only local perturbations. Consequently, the finding that the small stabilization by the mutation is completely reflected in an increased folding rate suggests that this region of the protein is as structured in the transition state as in the folded structure. It is therefore a target for engineering to increase the folding rate of the subdomain from approximately 0.5 micros(-1) for the nL mutant to the estimated theoretical speed limit of approximately 3 micros(-1).
  Selected figure(s)  
Figure 1.
Fig. 1. Structure of WT (pH 6.7). (a and b) Front (a) and back (b) views. Uncharged, acidic, and basic residues are shown in black, red, and blue, respectively. Lighter shades of the same color show alternate conformations. Dashed lines depict H bonds <3.5 Å. (c) Detail of the hydrophobic core. Van der Waals contacts <4 Å are depicted as dashed lines, with each Phe and its neighbors in the same color. For clarity, only side-chain or main-chain atoms of some residues and hydrogens of the core Phes are shown. (d) A representative region of the final 2 F[o] - F[c] map, contoured at 1.6 , showing density of D5-F6.
Figure 2.
Fig. 2. Comparison of x-ray and NMR structures. (a) 1VII (red) fitted to WT (pH 6.7) (green) by residues 1-34 with only selective side chains is shown. Dashed lines are H bonds as in Fig. 1. (b) The same structures are fitted by residues 23-33 to highlight their dramatic differences. (c) RMS fit as with a, but between WT (pH 6.7) (green) and 1QQV (red).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21360629 A.Reiner (2011).
Triplet-triplet energy transfer studies on conformational dynamics in peptides and a protein.
  J Pept Sci, 17, 413-419.  
21377472 C.N.Pace, H.Fu, K.L.Fryar, J.Landua, S.R.Trevino, B.A.Shirley, M.M.Hendricks, S.Iimura, K.Gajiwala, J.M.Scholtz, and G.R.Grimsley (2011).
Contribution of hydrophobic interactions to protein stability.
  J Mol Biol, 408, 514-528.  
21321226 J.K.Chung, M.C.Thielges, and M.D.Fayer (2011).
Dynamics of the folded and unfolded villin headpiece (HP35) measured with ultrafast 2D IR vibrational echo spectroscopy.
  Proc Natl Acad Sci U S A, 108, 3578-3583.  
21441105 T.Cellmer, M.Buscaglia, E.R.Henry, J.Hofrichter, and W.A.Eaton (2011).
Making connections between ultrafast protein folding kinetics and molecular dynamics simulations.
  Proc Natl Acad Sci U S A, 108, 6103-6108.  
20194774 A.Reiner, P.Henklein, and T.Kiefhaber (2010).
An unlocking/relocking barrier in conformational fluctuations of villin headpiece subdomain.
  Proc Natl Acad Sci U S A, 107, 4955-4960.  
20590175 C.Zhang, and J.Ma (2010).
Enhanced sampling and applications in protein folding in explicit solvent.
  J Chem Phys, 132, 244101.  
  21132120 D.C.Urbanek, D.Y.Vorobyev, A.L.Serrano, F.Gai, and R.M.Hochstrasser (2010).
The Two Dimensional Vibrational Echo of a Nitrile Probe of the Villin HP35 Protein.
  J Phys Chem Lett, 1, 3311-3315.  
20421891 G.R.Bowman, X.Huang, and V.S.Pande (2010).
Network models for molecular kinetics and their initial applications to human health.
  Cell Res, 20, 622-630.  
21081086 H.Lei, Y.Su, L.Jin, and Y.Duan (2010).
Folding network of villin headpiece subdomain.
  Biophys J, 99, 3374-3384.  
19412905 I.H.Lee, S.Y.Kim, and J.Lee (2010).
Dynamic folding pathway models of the villin headpiece subdomain (HP-36) structure.
  J Comput Chem, 31, 57-65.  
20000466 K.N.Hu, W.M.Yau, and R.Tycko (2010).
Detection of a transient intermediate in a rapid protein folding process by solid-state nuclear magnetic resonance.
  J Am Chem Soc, 132, 24-25.  
20444688 M.Li, C.Chen, D.R.Davies, and T.K.Chiu (2010).
Induced-fit mechanism for prolyl endopeptidase.
  J Biol Chem, 285, 21487-21495.
PDB codes: 3iuj 3iul 3ium 3iun 3iuq 3iur 3ivm
18615421 E.Luttmann, D.L.Ensign, V.Vaidyanathan, M.Houston, N.Rimon, J.Øland, G.Jayachandran, M.Friedrichs, and V.S.Pande (2009).
Accelerating molecular dynamic simulation on the cell processor and Playstation 3.
  J Comput Chem, 30, 268-274.  
19791846 G.R.Bowman, K.A.Beauchamp, G.Boxer, and V.S.Pande (2009).
Progress and challenges in the automated construction of Markov state models for full protein systems.
  J Chem Phys, 131, 124101.  
19513117 G.R.Bowman, and V.S.Pande (2009).
The roles of entropy and kinetics in structure prediction.
  PLoS One, 4, e5840.  
19337664 J.Kubelka (2009).
Time-resolved methods in biophysics. 9. Laser temperature-jump methods for investigating biomolecular dynamics.
  Photochem Photobiol Sci, 8, 499-512.  
19647001 K.N.Hu, R.H.Havlin, W.M.Yau, and R.Tycko (2009).
Quantitative determination of site-specific conformational distributions in an unfolded protein by solid-state nuclear magnetic resonance.
  J Mol Biol, 392, 1055-1073.  
19479944 L.Vugmeyster (2009).
Slow backbone dynamics of chicken villin headpiece subdomain probed by NMR C'-N cross-correlated relaxation.
  Magn Reson Chem, 47, 746-751.  
19425552 M.R.Bunagan, J.Gao, J.W.Kelly, and F.Gai (2009).
Probing the folding transition state structure of the villin headpiece subdomain via side chain and backbone mutagenesis.
  J Am Chem Soc, 131, 7470-7476.  
19843466 P.L.Freddolino, and K.Schulten (2009).
Common structural transitions in explicit-solvent simulations of villin headpiece folding.
  Biophys J, 97, 2338-2347.  
19618902 S.Bagchi, C.Falvo, S.Mukamel, and R.M.Hochstrasser (2009).
2D-IR experiments and simulations of the coupling between amide-I and ionizable side chains in proteins: application to the Villin headpiece.
  J Phys Chem B, 113, 11260-11273.  
19598233 W.Meng, B.Shan, Y.Tang, and D.P.Raleigh (2009).
Native like structure in the unfolded state of the villin headpiece helical subdomain, an ultrafast folding protein.
  Protein Sci, 18, 1692-1701.  
19045234 H.Lei, X.Deng, Z.Wang, and Y.Duan (2008).
The fast-folding HP35 double mutant has a substantially reduced primary folding free energy barrier.
  J Chem Phys, 129, 155104.  
18434500 J.Gao, and J.W.Kelly (2008).
Toward quantification of protein backbone-backbone hydrogen bonding energies: An energetic analysis of an amide-to-ester mutation in an alpha-helix within a protein.
  Protein Sci, 17, 1096-1101.  
19033473 J.Kubelka, E.R.Henry, T.Cellmer, J.Hofrichter, and W.A.Eaton (2008).
Chemical, physical, and theoretical kinetics of an ultrafast folding protein.
  Proc Natl Acad Sci U S A, 105, 18655-18662.  
18195374 J.S.Yang, S.Wallin, and E.I.Shakhnovich (2008).
Universality and diversity of folding mechanics for three-helix bundle proteins.
  Proc Natl Acad Sci U S A, 105, 895-900.  
18922715 K.R.Thurber, and R.Tycko (2008).
Biomolecular solid state NMR with magic-angle spinning at 25K.
  J Magn Reson, 195, 179-186.  
18820237 L.Vugmeyster, and C.J.McKnight (2008).
Slow motions in chicken villin headpiece subdomain probed by cross-correlated NMR relaxation of amide NH bonds in successive residues.
  Biophys J, 95, 5941-5950.  
19020085 T.Cellmer, E.R.Henry, J.Hofrichter, and W.A.Eaton (2008).
Measuring internal friction of an ultrafast-folding protein.
  Proc Natl Acad Sci U S A, 105, 18320-18325.  
18284690 W.Gronwald, T.Hohm, and D.Hoffmann (2008).
Evolutionary Pareto-optimization of stably folding peptides.
  BMC Bioinformatics, 9, 109.
PDB code: 2ppz
17704172 D.Du, M.R.Bunagan, and F.Gai (2007).
The effect of charge-charge interactions on the kinetics of alpha-helix formation.
  Biophys J, 93, 4076-4082.  
17123960 G.Cornilescu, E.B.Hadley, M.G.Woll, J.L.Markley, S.H.Gellman, and C.C.Cornilescu (2007).
Solution structure of a small protein containing a fluorinated side chain in the core.
  Protein Sci, 16, 14-19.
PDB code: 2jm0
17360390 H.Lei, C.Wu, H.Liu, and Y.Duan (2007).
Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations.
  Proc Natl Acad Sci U S A, 104, 4925-4930.  
17512537 H.Lei, and Y.Duan (2007).
Two-stage folding of HP-35 from ab initio simulations.
  J Mol Biol, 370, 196-206.  
16963648 S.Jang, N.Sreerama, V.H.Liao, S.H.Lu, F.Y.Li, S.Shin, R.W.Woody, and S.H.Lin (2006).
Theoretical investigation of the photoinitiated folding of HP-36.
  Protein Sci, 15, 2290-2299.  
16689642 Y.Levy, and J.N.Onuchic (2006).
Water mediation in protein folding and molecular recognition.
  Annu Rev Biophys Biomol Struct, 35, 389-415.  
16354298 F.Fogolari, S.C.Tosatto, and G.Colombo (2005).
A decoy set for the thermostable subdomain from chicken villin headpiece, comparison of different free energy estimators.
  BMC Bioinformatics, 6, 301.  
16392943 J.M.Carr, and D.J.Wales (2005).
Global optimization and folding pathways of selected alpha-helical proteins.
  J Chem Phys, 123, 234901.  
16269546 S.H.Brewer, D.M.Vu, Y.Tang, Y.Li, S.Franzen, D.P.Raleigh, and R.B.Dyer (2005).
Effect of modulating unfolded state structure on the folding kinetics of the villin headpiece subdomain.
  Proc Natl Acad Sci U S A, 102, 16662-16667.  
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.