PDBsum entry 2r15

Contractile protein

PDB id: 2r15

Contents

Protein chain

207 a.a. *

Ligands

ACT

GOL ×3

Waters ×247

* Residue conservation analysis

PDB id:

2r15

Name:

Contractile protein

Title:

Crystal structure of the myomesin domains 12 and 13

Structure:

Myomesin-1. Chain: a, b. Fragment: domains 12 and 13, unp residues 1225-1443. Synonym: 190 kda titin-associated protein, 190 kda connectin- associated protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: myom1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.24Å R-factor: 0.196 R-free: 0.223

Authors:

N.Pinotsis,M.Wilmanns,S.Lange

Key ref:

N.Pinotsis et al. (2008). Molecular basis of the C-terminal tail-to-tail assembly of the sarcomeric filament protein myomesin. EMBO J, 27, 253-264. PubMed id: 18059477 DOI: 10.1038/sj.emboj.7601944

Date:

22-Aug-07 Release date: 29-Jan-08

Protein chains

P52179  (MYOM1_HUMAN) -  Myomesin-1 from Homo sapiens

Seq: 1685 a.a.

Struc: 207 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/sj.emboj.7601944

EMBO J 27:253-264 (2008)

PubMed id: 18059477

Molecular basis of the C-terminal tail-to-tail assembly of the sarcomeric filament protein myomesin.

N.Pinotsis, S.Lange, J.C.Perriard, D.I.Svergun, M.Wilmanns.

ABSTRACT

Sarcomeric filament proteins display extraordinary properties in terms of protein length and mechanical elasticity, requiring specific anchoring and assembly mechanisms. To establish the molecular basis of terminal filament assembly, we have selected the sarcomeric M-band protein myomesin as a prototypic filament model. The crystal structure of the myomesin C-terminus, comprising a tandem array of two immunoglobulin (Ig) domains My12 and My13, reveals a dimeric end-to-end filament of 14.3 nm length. Although the two domains share the same fold, an unexpected rearrangement of one beta-strand reveals how they are evolved into unrelated functions, terminal filament assembly (My13) and filament propagation (My12). The two domains are connected by a six-turn alpha-helix, of which two turns are void of any interactions with other protein parts. Thus, the overall structure of the assembled myomesin C-terminus resembles a three-body beads-on-the-string model with potentially elastic properties. We predict that the found My12-helix-My13 domain topology may provide a structural template for the filament architecture of the entire C-terminal Ig domain array My9-My13 of myomesin.

Selected figure(s)

Figure 3.
Figure 3 Semitransparent surface presentation of (A) My12 and (B) My13. The interface areas with the My12–My13-connecting helix and the My13 dimerization interface are colored in green and blue, respectively, demonstrating overlapping interface areas in My12 and My13. The ribbon of each domain is in gray, except -strand A' (yellow) that swaps in My12 in terms of -sheet association. Those structural elements that are involved in interface surfaces are labeled.

Figure 8.
Figure 8 Prediction of a myomesin filament beads-on-the-string model, consisting of 2 5 Ig domains that are connected by -helical linkers and end-to-end C-terminal assembly. (A) Beads-on-the-string presentation of the crystal structure of the My12–My13 dimeric assembly of the myomesin C-terminus (cp. Figure 1). (B) Schematic model of the My9–My13 C-terminal filament, in which adjacent domains are connected by -helical linkers. (C) Prediction of -helical segments at repetitive sequence intervals, interspersed myomesin domains My9, My10, My11, My12 and My13, using PredictProtein (Rost et al, 2004). The starting residue number, the sequence interval with respect to the previous predicted -helical segment and the sequence of each predicted -helix segment are presented. Residues that are predicted to be -helical by PROF (for details, see PredictProtein) are shown in capital characters, and those that are predicted with a confidence level of at least 82% are shown by small characters. The predicted helix length, using the two categories, is indicated (second number in parentheses). For comparison, the experimentally determined My12–My13-connecting helix is highlighted in green. (D) Circular dichroism curves of My12–My13 (blue) and My9–My13 (magenta). The estimates for secondary structural elements for My12–My13 and My9–My13 are as follows: helix, 0.23/0.19; strand, 0.26/0.36; turn, 0.18/0.13; unordered, 0.33/0.34.

The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2008, 27, 253-264) copyright 2008.

Figures were selected by an automated process.