PDBsum entry 1myo

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protein links
Ank-repeat PDB id
Protein chain
118 a.a. *
* Residue conservation analysis
PDB id:
Name: Ank-repeat
Title: Solution structure of myotrophin, nmr, 44 structures
Structure: Myotrophin. Chain: a
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: heart
NMR struc: 44 models
Authors: Y.Yang,S.Nanduri,S.Sen,J.Qin
Key ref:
Y.Yang et al. (1998). The structural basis of ankyrin-like repeat function as revealed by the solution structure of myotrophin. Structure, 6, 619-626. PubMed id: 9634699 DOI: 10.1016/S0969-2126(98)00063-X
17-Aug-98     Release date:   17-Aug-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P62775  (MTPN_RAT) -  Myotrophin
118 a.a.
118 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   6 terms 
  Biological process     regulation of barbed-end actin filament capping   12 terms 
  Biochemical function     protein binding     1 term  


DOI no: 10.1016/S0969-2126(98)00063-X Structure 6:619-626 (1998)
PubMed id: 9634699  
The structural basis of ankyrin-like repeat function as revealed by the solution structure of myotrophin.
Y.Yang, S.Nanduri, S.Sen, J.Qin.
BACKGROUND: Myotrophin is a 12.5 kDa protein that appears to have a key role in the initiation of cardiac hypertrophy, a central process in many heart diseases. Myotrophin primarily comprises ankyrin-like (ANK) repeats, the 33 amino acid motifs involved in a wide range of protein-protein interactions. As a first step in the structure-based search for cardiac hypertrophy antagonists and in order to gain insight into the molecular basis of action of the ubiquitous and multifunctional ANK repeat motif, we have determined the solution structure of myotrophin using multidimensional heteronuclear NMR spectroscopy. RESULTS: The myotrophin structure determination was based on 2786 experimental NMR restraints, and the precision of the coordinates for the final 45 simulated-annealing structures is 0.43 A for the backbone atoms and 0.87 A for all atoms. The structure of myotrophin is well defined and is ellipsoidal: approximately 46 A long and 21 A wide. The ANK repeats, which constitute the main part of the myotrophin structure, are characteristic of a hairpin-like protruding tip followed by a helix-turn-helix motif. The V-shaped helix-turn-helix of the ANK repeats stack sequentially in bundles and are stabilized by compact hydrophobic cores, whereas the protruding tips are less ordered. This arrangement is quite different to the continuous beta-sheet topology observed in the corresponding regions of another ANK protein, 53BP2, the structure of which was determined in complex with p53. CONCLUSIONS: The solution structure of myotrophin provides important insights into the structural and dynamic features of the ANK motif, and suggests that the protruding tips with highly variable sequences may be critical to facilitate diverse protein-protein recognition. The present structure also provides a molecular basis for the further functional characterization of myotrophin and the development of therapeutics for hypertrophy-related heart diseases.
  Selected figure(s)  
Figure 5.
Figure 5. The overall fold of myotrophin and comparisons with 53BP2. (a) Ribbon representation of the myotrophin structure. All helices are labeled sequentially (a1, a2, a3, a4, a5, a6, a7 and a8). The structure is primarily composed of four sequential helix-turn-helix motifs stacked as helix bundles. It is clear that all the helices lie on one side of the protein, whereas the loops including those from the ANK repeats protrude to the other side of the protein, and are likely to be involved in protein recognition. (b) Structural comparisons of the ANK repeats of myotrophin and 53BP2. The superposition of ANK 1 (green) and ANK 2 of myotrophin (blue) onto ANK 2 (purple) and ANK 3 (purple) of 53BP2, respectively. Although the fold of each repeat is similar to those of 53BP2, the protruding tips from the two repeats of myotrophin do not interact with each other and are less well ordered. This is in contrast to the continuous b sheet formed by the corresponding regions in 53BP2 complexed with p53 [11]. The dynamics of the ANK repeats in myotrophin were found to be different from those of 53BP2 [10]. The protruding tips with highly variable sequences may be critical in controlling diverse functions of various ANK repeat-bearing proteins. (The figures were prepared with the program MOLSCRIPT [25].)
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 619-626) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20625546 S.Takeda, S.Minakata, R.Koike, I.Kawahata, A.Narita, M.Kitazawa, M.Ota, T.Yamakuni, Y.Maéda, and Y.Nitanai (2010).
Two distinct mechanisms for actin capping protein regulation--steric and allosteric inhibition.
  PLoS Biol, 8, e1000416.
PDB codes: 3aa0 3aa1 3aa6 3aa7 3aaa
19591507 C.F.Cervantes, P.R.Markwick, S.C.Sue, J.A.McCammon, H.J.Dyson, and E.A.Komives (2009).
Functional dynamics of the folded ankyrin repeats of I kappa B alpha revealed by nuclear magnetic resonance.
  Biochemistry, 48, 8023-8031.  
18693253 B.Das, S.Gupta, A.Vasanji, Z.Xu, S.Misra, and S.Sen (2008).
Nuclear Co-translocation of Myotrophin and p65 Stimulates Myocyte Growth: REGULATION BY MYOTROPHIN HAIRPIN LOOPS.
  J Biol Chem, 283, 27947-27956.  
17174335 D.U.Ferreiro, C.F.Cervantes, S.M.Truhlar, S.S.Cho, P.G.Wolynes, and E.A.Komives (2007).
Stabilizing IkappaBalpha by "consensus" design.
  J Mol Biol, 365, 1201-1216.  
16895918 N.Bhattacharya, S.Ghosh, D.Sept, and J.A.Cooper (2006).
Binding of myotrophin/V-1 to actin-capping protein: implications for how capping protein binds to the filament barbed end.
  J Biol Chem, 281, 31021-31030.  
16054028 C.Yang, M.Pring, M.A.Wear, M.Huang, J.A.Cooper, T.M.Svitkina, and S.H.Zigmond (2005).
Mammalian CARMIL inhibits actin filament capping by capping protein.
  Dev Cell, 9, 209-221.  
16276529 M.Huang, M.Pring, C.Yang, M.Taoka, and S.H.Zigmond (2005).
Presence of a novel inhibitor of capping protein in neutrophil extract.
  Cell Motil Cytoskeleton, 62, 232-243.  
15215520 C.H.Croy, S.Bergqvist, T.Huxford, G.Ghosh, and E.A.Komives (2004).
Biophysical characterization of the free IkappaBalpha ankyrin repeat domain in solution.
  Protein Sci, 13, 1767-1777.  
12566564 A.Kohl, H.K.Binz, P.Forrer, M.T.Stumpp, A.Plückthun, and M.G.Grütter (2003).
Designed to be stable: crystal structure of a consensus ankyrin repeat protein.
  Proc Natl Acad Sci U S A, 100, 1700-1705.
PDB code: 1mj0
12517341 K.S.Tang, A.R.Fersht, and L.S.Itzhaki (2003).
Sequential unfolding of ankyrin repeats in tumor suppressor p16.
  Structure, 11, 67-73.  
12488317 M.Taoka, T.Ichimura, A.Wakamiya-Tsuruta, Y.Kubota, T.Araki, T.Obinata, and T.Isobe (2003).
V-1, a protein expressed transiently during murine cerebellar development, regulates actin polymerization via interaction with capping protein.
  J Biol Chem, 278, 5864-5870.  
12686541 S.Malek, D.B.Huang, T.Huxford, S.Ghosh, and G.Ghosh (2003).
X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex.
  J Biol Chem, 278, 23094-23100.
PDB codes: 1k3z 1oy3
11971907 P.Knuefermann, P.Chen, A.Misra, S.P.Shi, M.Abdellatif, and N.Sivasubramanian (2002).
Myotrophin/V-1, a protein up-regulated in the failing human heart and in postnatal cerebellum, converts NFkappa B p50-p65 heterodimers to p50-p50 and p65-p65 homodimers.
  J Biol Chem, 277, 23888-23897.  
12456646 P.Michaely, D.R.Tomchick, M.Machius, and R.G.Anderson (2002).
Crystal structure of a 12 ANK repeat stack from human ankyrinR.
  EMBO J, 21, 6387-6396.
PDB code: 1n11
10431175 S.G.Sedgwick, and S.J.Smerdon (1999).
The ankyrin repeat: a diversity of interactions on a common structural framework.
  Trends Biochem Sci, 24, 311-316.  
9782052 R.Baumgartner, C.Fernandez-Catalan, A.Winoto, R.Huber, R.A.Engh, and T.A.Holak (1998).
Structure of human cyclin-dependent kinase inhibitor p19INK4d: comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16INK4a.
  Structure, 6, 1279-1290.
PDB code: 1bd8
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.