PDBsum entry 2fxo

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protein Protein-protein interface(s) links
Contractile protein PDB id
Protein chains
129 a.a. *
* Residue conservation analysis
PDB id:
Name: Contractile protein
Title: Structure of the human beta-myosin s2 fragment
Structure: Myosin heavy chain, cardiac muscle beta isoform. Chain: a, b, c, d. Fragment: delta-s2 fragment (838-963). Synonym: beta-myosin, myhc-beta. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: heart muscle. Gene: hsbmhc. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.277     R-free:   0.349
Authors: W.Blankenfeldt,N.H.Thoma,J.S.Wray,M.Gautel,I.Schlichting
Key ref:
W.Blankenfeldt et al. (2006). Crystal structures of human cardiac beta-myosin II S2-Delta provide insight into the functional role of the S2 subfragment. Proc Natl Acad Sci U S A, 103, 17713-17717. PubMed id: 17095604 DOI: 10.1073/pnas.0606741103
06-Feb-06     Release date:   21-Nov-06    
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Protein chains
Pfam   ArchSchema ?
Q5GJ54  (Q5GJ54_HUMAN) -  Rhabdomyosarcoma antigen MU-RMS-40.7B (Fragment)
1179 a.a.
129 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)


DOI no: 10.1073/pnas.0606741103 Proc Natl Acad Sci U S A 103:17713-17717 (2006)
PubMed id: 17095604  
Crystal structures of human cardiac beta-myosin II S2-Delta provide insight into the functional role of the S2 subfragment.
W.Blankenfeldt, N.H.Thomä, J.S.Wray, M.Gautel, I.Schlichting.
Myosin II is the major component of the muscle thick filament. It consists of two N-terminal S1 subfragments ("heads") connected to a long dimeric coiled-coil rod. The rod is in itself twofold symmetric, but in the filament, the two heads point away from the filament surface and are therefore not equivalent. This breaking of symmetry requires the initial section of the rod, subfragment 2 (S2), to be relatively flexible. S2 is an important functional element, involved in various mechanisms by which the activity of smooth and striated muscle is regulated. We have determined crystal structures of the 126 N-terminal residues of S2 from human cardiac beta-myosin II (S2-Delta), of both WT and the disease-associated E924K mutant. S2-Delta is a straight parallel dimeric coiled coil, but the N terminus of one chain is disordered in WT-S2-Delta due to crystal contacts, indicative of unstable local structure. Bulky noncanonical side chains pack into a/d positions of S2-Delta's N terminus, leading to defined local asymmetry and axial stagger, which could induce nonequivalence of the S1 subfragments. Additionally, S2 possesses a conserved charge distribution with three prominent rings of negative potential within S2-Delta, the first of which may provide a binding interface for the "blocked head" of smooth muscle myosin in the OFF state. The observation that many disease-associated mutations affect the second negatively charged ring further suggests that charge interactions play an important role in regulation of cardiac muscle activity through myosin-binding protein C.
  Selected figure(s)  
Figure 2.
Fig. 2. Ribbon plots of the asymmetric unit of (A) WT-S2- and (B) E924K-S2- . N designates the N terminus. Light-gray ribbons depict crystallographic neighbors. In A, dark-gray spheres show the position of two mercury atoms bound to C905 and C947. The pink helical coil indicates the position of residual electron density at the flexible N terminus of the chain in magenta. All molecular representations were prepared with PyMOL (34).
Figure 4.
Fig. 4. Model of the OFF state, based on the structure of S2- , a model of smooth muscle myosin in the 10S conformation (29) and the cryo-EM reconstruction of tarantula thick filament (2). The model was constructed by introducing a single bent at position 877 into S2- . The electrostatic surface potential of S2- was calculated with APBS (36). The blocked head is shown in yellow with the amino acids framing loop 2 shown in magenta, although the actual residues of loop 2 are missing. The remaining residues of the approximate actin-binding interface have been colored in dark green (37). (Inset) Magnification of the interaction after a clockwise 90° rotation around the coiled-coil main axis. For an unobstructed view, the free head has been omitted.
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20399176 A.Hinz, N.Miguet, G.Natrajan, Y.Usami, H.Yamanaka, P.Renesto, B.Hartlieb, A.A.McCarthy, J.P.Simorre, H.Göttlinger, and W.Weissenhorn (2010).
Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain.
  Cell Host Microbe, 7, 314-323.
PDB code: 2x7a
20385845 V.Nucciotti, C.Stringari, L.Sacconi, F.Vanzi, L.Fusi, M.Linari, G.Piazzesi, V.Lombardi, and F.S.Pavone (2010).
Probing myosin structural conformation in vivo by second-harmonic generation microscopy.
  Proc Natl Acad Sci U S A, 107, 7763-7768.  
19805198 J.Yang, Y.Q.Ma, R.C.Page, S.Misra, E.F.Plow, and J.Qin (2009).
Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.
  Proc Natl Acad Sci U S A, 106, 17729-17734.
PDB code: 2knc
18926831 A.Ababou, E.Rostkova, S.Mistry, C.Le Masurier, M.Gautel, and M.Pfuhl (2008).
Myosin binding protein C positioned to play a key role in regulation of muscle contraction: structure and interactions of domain C1.
  J Mol Biol, 384, 615-630.
PDB code: 2avg
18323455 C.McNamara, A.S.Zinkernagel, P.Macheboeuf, M.W.Cunningham, V.Nizet, and P.Ghosh (2008).
Coiled-coil irregularities and instabilities in group A Streptococcus M1 are required for virulence.
  Science, 319, 1405-1408.
PDB code: 2oto
18495867 H.S.Jung, S.Komatsu, M.Ikebe, and R.Craig (2008).
Head-head and head-tail interaction: a general mechanism for switching off myosin II activity in cells.
  Mol Biol Cell, 19, 3234-3242.  
18234833 I.Adamovic, S.M.Mijailovich, and M.Karplus (2008).
The elastic properties of the structurally characterized myosin II S2 subdomain: a molecular dynamics and normal mode analysis.
  Biophys J, 94, 3779-3789.  
18155233 J.H.Brown, Y.Yang, L.Reshetnikova, S.Gourinath, D.Süveges, J.Kardos, F.Hóbor, R.Reutzel, L.Nyitray, and C.Cohen (2008).
An unstable head-rod junction may promote folding into the compact off-state conformation of regulated myosins.
  J Mol Biol, 375, 1434-1443.
PDB codes: 3bas 3bat
18951904 L.Alamo, W.Wriggers, A.Pinto, F.Bártoli, L.Salazar, F.Q.Zhao, R.Craig, and R.Padrón (2008).
Three-dimensional reconstruction of tarantula myosin filaments suggests how phosphorylation may regulate myosin activity.
  J Mol Biol, 384, 780-797.
PDB code: 3dtp
18555187 M.Buvoli, M.Hamady, L.A.Leinwand, and R.Knight (2008).
Bioinformatics assessment of beta-myosin mutations reveals myosin's high sensitivity to mutations.
  Trends Cardiovasc Med, 18, 141-149.  
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.