Our homology models of human beta-cardiac myosin with their heads folded back onto their own S2 tail can be downloaded below.  Such folded-back structures have been referred to in publications by others as the interacting-heads motif (IHM) since there are interactions between the heads in addition to interactions between the heads and S2.  Our homology models consist of complete sequences of heavy chain and human ventricular cardiac myosin regulatory (RLC) and essential (ELC) light chains.  They have all been energy minimized using the YASARA force field.  We hope you find them useful in your work, and we only ask that if you use these models in your publications or your seminars that you acknowledge their origins from the Spudich laboratory.


We have created three homology models, MS01, MS02 and MS03, all of which are very similar to one another and are all consistent with the conclusions and considerations discussed in our 2016 and 2017 publications.  All three models receive a good evaluation score by the evaluation metrics TSVMod scores, Z-score (DOPE), GA341 scores as described at
https://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/modbase.html

Click on the file name below to download the file.

MS01

MS01C0C2

MS01C0C10

MS02

MS03


Descriptions of these homology models and how they were made:

Our MS01 folded-back human beta-cardiac complete sequence model is described in Nag et al. (ref 1). It was built by Dr. Margaret Sunitha using the PDB 3DTP tarantula skeletal myosin heavy chain 2-nm resolution EM-reconstructed folded-back structure of Alamo et al. (ref 2) as template, and the human cardiac ventricular light chains that were modeled by Dr. Sunitha earlier (ref 3) were aligned to the light chains of the tarantula template structure to obtain the full model. The modeling protocol is described in Nag et al. (ref 1).

MS01: A complete folded-back model of human beta-cardiac myosin with human cardiac light chains

MS01: A complete folded-back model of human beta-cardiac myosin with human cardiac light chains

  1. Nag, S., Trivedi, D.V. et al. The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nat. Struct. Mol. Biol., in press (2017).
  2. Alamo, L. et al. Three-dimensional reconstruction of tarantula myosin filaments suggests how phosphorylation may regulate myosin activity. J. Mol. Biol. 384, 780–797 (2008).
  3. Homburger, J.R. et al. Multidimensional structure-function relationships in human beta-cardiac myosin from population-scale genetic variation. Proc. Natl. Acad. Sci. USA 113, 6701–6706 (2016). 

Our MS01C0C2 and MS01C0C10 folded-back human beta-cardiac complete sequence models with the C0-C2 N-terminal fragment of myosin binding protein-C (MyBP-C) or full length (C0-C10 domains) MyBP-C bound to the MS01 folded back myosin structure are described in Nag et al. (ref 1).  These hypothetical structures are based on known biochemical interactions of MyBP-C with myosin and serve the purpose of working models for biochemical experiments going forward.  The MyBP-C domains shown are homology-modeled structures of cardiac MyBP-C domains by Dr. Margaret Sunitha. The MS01C0C2 and MS01C0C10 models were built by manually positioning the MyBP-C domains onto the MS01 myosin structure using PyMOL.

                   MS01C0C2                                    MS01C0C10    

                   MS01C0C2                                    MS01C0C10    

1. Nag, S., Trivedi, D.V. et al. The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nat. Struct. Mol. Biol., in press (2017).


Our MS02 folded-back human beta-cardiac complete sequence model was built by Dr. Margaret Sunitha using the PDB 3DTP tarantula skeletal myosin heavy chain 2-nm resolution EM reconstructed folded-back structure of Alamo et al. (ref 1) as template using both the heavy and the light chains, and the human cardiac ventricular light chains that were modeled earlier (ref 2) were used as additional templates to minimize steric clashes. The modeling protocol was similar to Homburger, J.R. et al. (ref 2).  While the MS01 and MS02 models are the same with respect to all of the conclusions and considerations discussed in our recent papers (refs 3-5), the MS02 version eliminates minor steric clashes between the LCs and the blocked-head heavy chain that occur in MS01.

1. Alamo, L. et al. Three-dimensional reconstruction of tarantula myosin filaments suggests how phosphorylation may regulate myosin activity. J. Mol. Biol. 384, 780–797 (2008).                                                   2. Homburger, J.R. et al. Multidimensional structure-function relationships in human beta-cardiac myosin from population-scale genetic variation. Proc. Natl. Acad. Sci. USA 113, 6701–6706 (2016).                                       3. Adhikari, A.S. et al. Early-onset cardiomyopathy mutations significantly increase the velocity, force and actin-activated ATPase activity of human beta-cardiac myosin. Cell Rep. 17, 2857-2864 (2016).                           4. Kawana, M. et al. Biophysical properties of human beta-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy. Sci. Adv. 3, e1601959 (2017).                                                                                         5. Nag, S., Trivedi, D.V. et al. The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nat. Struct. Mol. Biol., in press (2017).


Our MS03 folded-back human beta-cardiac complete sequence model was built by Dr. Margaret Sunitha using the PDB 3JBH tarantula skeletal myosin heavy chain 2-nm resolution EM reconstructed folded-back structure of Alamo et al. (ref 1) as template using both the heavy and the light chains, and the human cardiac ventricular light chains that were modeled earlier (ref 2) were used as additional templates. The modeling protocol was similar to Homburger, J.R. et al. (ref 2).  The MS01, MS02 and MS03 models are the same with respect to all of the conclusions and considerations discussed in our recent papers (refs 3-5).

1. Alamo, L. et al. Conserved intramolecular interactions maintain myosin interacting-heads motifs explaining tarantula muscle super-relaxed state structural basis. J. Mol. Biol. 428, 1142-1164 (2016).                                   2. Homburger, J.R. et al. Multidimensional structure-function relationships in human beta-cardiac myosin from population-scale genetic variation. Proc. Natl. Acad. Sci. USA 113, 6701–6706 (2016).                                       3. Adhikari, A.S. et al. Early-onset cardiomyopathy mutations significantly increase the velocity, force and actin-activated ATPase activity of human beta-cardiac myosin. Cell Rep. 17, 2857-2864 (2016).                           4. Kawana, M. et al. Biophysical properties of human beta-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy. Sci. Adv. 3, e1601959 (2017).                                                                                         5. Nag, S., Trivedi, D.V. et al. The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nat. Struct. Mol. Biol., in press (2017).