PDBsum entry 2wp3

Transferase/structural protein

PDB id

2wp3

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Contents

			Protein chains

					97 a.a. *


					99 a.a. *

			Ligands

					GOL ×4


					SO4

			Waters ×233

* Residue conservation analysis

PDB id:

2wp3

Links

Name:

Transferase/structural protein

Title:

Crystal structure of the titin m10-obscurin like 1 ig complex

Structure:

Obscurin-like protein 1. Chain: o. Fragment: ig1, residues 1-106. Engineered: yes. Titin. Chain: t. Fragment: m10, residues 34252-34350. Synonym: connectin, rhabdomysarcoma antigen mu-rms-40.14. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.48Å

R-factor:

0.178

R-free:

0.217

Authors:

S.Pernigo,A.Fuzukawa,M.Gautel,R.A.Steiner

Key ref:

S.Pernigo et al. (2010). Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex. Proc Natl Acad Sci U S A, 107, 2908-2913. PubMed id: 20133654

Date:

02-Aug-09

Release date:

16-Feb-10

PROCHECK

	Headers

	References

Protein chain

O75147 (OBSL1_HUMAN) - Obscurin-like protein 1 from Homo sapiens

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Seq: Struc:					1896 a.a. 97 a.a.

Protein chain

Q8WZ42 (TITIN_HUMAN) - Titin from Homo sapiens

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Seq: Struc:					34350 a.a. 99 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

Chain T: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

1.	L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
2.	L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein]	+	ATP	=	O-phospho-L-seryl-[protein]	+	ADP	+	H(+)

L-threonyl-[protein]	+	ATP	=	O-phospho-L-threonyl-[protein]	+	ADP	+	H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

	Proc Natl Acad Sci U S A 107:2908-2913 (2010)
PubMed id: 20133654

Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex.
S.Pernigo, A.Fukuzawa, M.Bertz, M.Holt, M.Rief, R.A.Steiner, M.Gautel.

ABSTRACT

In the sarcomeric M-band, the giant ruler proteins titin and obscurin, its small homologue obscurin-like-1 (obsl1), and the myosin cross-linking protein myomesin form a ternary complex that is crucial for the function of the M-band as a mechanical link. Mutations in the last titin immunoglobulin (Ig) domain M10, which interacts with the N-terminal Ig-domains of obscurin and obsl1, lead to hereditary muscle diseases. The M10 domain is unusual not only in that it is a frequent target of disease-linked mutations, but also in that it is the only currently known muscle Ig-domain that interacts with two ligands--obscurin and obsl1--in different sarcomeric subregions. Using x-ray crystallography, we show the structural basis for titin M10 interaction with obsl1 in a novel antiparallel Ig-Ig architecture and unravel the molecular basis of titin-M10 linked myopathies. The severity of these pathologies correlates with the disruption of the titin-obsl1/obscurin complex. Conserved signature residues at the interface account for differences in affinity that direct the cellular sorting in cardiomyocytes. By engineering the interface signature residues of obsl1 to obscurin, and vice versa, their affinity for titin can be modulated similar to the native proteins. In single-molecule force-spectroscopy experiments, both complexes yield at forces of around 30 pN, much lower than those observed for the mechanically stable Z-disk complex of titin and telethonin, suggesting why even moderate weakening of the obsl1/obscurin-titin links has severe consequences for normal muscle functions.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21190822

M.Gautel (2011).
The sarcomeric cytoskeleton: who picks up the strain?

Curr Opin Cell Biol, 23, 39-46.

21185285

S.Perera, M.R.Holt, B.S.Mankoo, and M.Gautel (2011).
Developmental regulation of MURF ubiquitin ligases and autophagy proteins nbr1, p62/SQSTM1 and LC3 during cardiac myofibril assembly and turnover.

Dev Biol, 351, 46-61.

20855473

K.Charton, N.Danièle, A.Vihola, C.Roudaut, E.Gicquel, F.Monjaret, A.Tarrade, J.Sarparanta, B.Udd, and I.Richard (2010).
Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies.

Hum Mol Genet, 19, 4608-4624.

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.