PDBsum entry 1myo

Ank-repeat

PDB id: 1myo

Contents

Protein chain

118 a.a. *

* Residue conservation analysis

PDB id:

1myo

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

Date:

17-Aug-98 Release date: 17-Aug-99

Protein chain

P62775  (MTPN_RAT) -  Myotrophin from Rattus norvegicus

Seq: 118 a.a.

Struc: 118 a.a.

Enzyme reactions

• Enzyme class: E.C.?

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.

ABSTRACT

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.