The elastic I-band region of titin is assembled in a "modular" fashion by weakly interacting Ig-like domains

A. S. Politou, M. Gautel, S. Improta, L. Vangelista, A. Pastore

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The vertebrate striated muscle protein titin is thought to play a critical rôle in myofibril assembly and passive tension. The recently determined complete primary structure of titin revealed a modular architecture that opens the way to a structural characterisation and the understanding of essential properties of this molecule through dissection into units that are structurally and/or functionally relevant. To understand the assembly process of titin, and ultimately the molecular basis of its elastic behaviour, we studied the thermodynamic properties of module pairs, the smallest structural unit that includes a module-module interface. Thus, selected module pairs and their component single modules from the I-band part of the titin molecule were expressed in Escherichia coli and their heat-induced and denaturant-induced unfolding was investigated with a combination of techniques (circular dichroism, fluorescence spectroscopy and nuclear magnetic resonance). The stabilities of single modules and pairs were determined from denaturation experiments. The module interface was also modelled on the basis of the sequence alignment of all ∼40 immunoglobulin like modules from the I-band and the known structure of one of them. Our results show that all modules and module pairs examined are independently folded in solution. When covalently linked, although weakly interacting, they still behave as autonomous co-operative units upon unfolding. These observations lead us to suggest that folding of titin in vitro is a hierarchical event and that weak interactions between its adjacent modules must only partly account for its presumed elastic function.

Original languageEnglish
Pages (from-to)604-616
Number of pages13
JournalJournal of Molecular Biology
Volume255
Issue number4
DOIs
Publication statusPublished - Feb 2 1996
Externally publishedYes

Fingerprint

Connectin
Striated Muscle
Muscle Proteins
Myofibrils
Sequence Alignment
Fluorescence Spectrometry
Circular Dichroism
Thermodynamics
Vertebrates
Dissection
Immunoglobulins
Magnetic Resonance Spectroscopy
Hot Temperature
Immunoglobulin Domains
Escherichia coli

Keywords

  • Connectin
  • Elasticity
  • Interface
  • Module
  • Muscle
  • Unfolding

ASJC Scopus subject areas

  • Virology

Cite this

The elastic I-band region of titin is assembled in a "modular" fashion by weakly interacting Ig-like domains. / Politou, A. S.; Gautel, M.; Improta, S.; Vangelista, L.; Pastore, A.

In: Journal of Molecular Biology, Vol. 255, No. 4, 02.02.1996, p. 604-616.

Research output: Contribution to journalArticle

Politou, A. S. ; Gautel, M. ; Improta, S. ; Vangelista, L. ; Pastore, A. / The elastic I-band region of titin is assembled in a "modular" fashion by weakly interacting Ig-like domains. In: Journal of Molecular Biology. 1996 ; Vol. 255, No. 4. pp. 604-616.
@article{294412349e124b2586454371a394cc23,
title = "The elastic I-band region of titin is assembled in a {"}modular{"} fashion by weakly interacting Ig-like domains",
abstract = "The vertebrate striated muscle protein titin is thought to play a critical r{\^o}le in myofibril assembly and passive tension. The recently determined complete primary structure of titin revealed a modular architecture that opens the way to a structural characterisation and the understanding of essential properties of this molecule through dissection into units that are structurally and/or functionally relevant. To understand the assembly process of titin, and ultimately the molecular basis of its elastic behaviour, we studied the thermodynamic properties of module pairs, the smallest structural unit that includes a module-module interface. Thus, selected module pairs and their component single modules from the I-band part of the titin molecule were expressed in Escherichia coli and their heat-induced and denaturant-induced unfolding was investigated with a combination of techniques (circular dichroism, fluorescence spectroscopy and nuclear magnetic resonance). The stabilities of single modules and pairs were determined from denaturation experiments. The module interface was also modelled on the basis of the sequence alignment of all ∼40 immunoglobulin like modules from the I-band and the known structure of one of them. Our results show that all modules and module pairs examined are independently folded in solution. When covalently linked, although weakly interacting, they still behave as autonomous co-operative units upon unfolding. These observations lead us to suggest that folding of titin in vitro is a hierarchical event and that weak interactions between its adjacent modules must only partly account for its presumed elastic function.",
keywords = "Connectin, Elasticity, Interface, Module, Muscle, Unfolding",
author = "Politou, {A. S.} and M. Gautel and S. Improta and L. Vangelista and A. Pastore",
year = "1996",
month = "2",
day = "2",
doi = "10.1006/jmbi.1996.0050",
language = "English",
volume = "255",
pages = "604--616",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - The elastic I-band region of titin is assembled in a "modular" fashion by weakly interacting Ig-like domains

AU - Politou, A. S.

AU - Gautel, M.

AU - Improta, S.

AU - Vangelista, L.

AU - Pastore, A.

PY - 1996/2/2

Y1 - 1996/2/2

N2 - The vertebrate striated muscle protein titin is thought to play a critical rôle in myofibril assembly and passive tension. The recently determined complete primary structure of titin revealed a modular architecture that opens the way to a structural characterisation and the understanding of essential properties of this molecule through dissection into units that are structurally and/or functionally relevant. To understand the assembly process of titin, and ultimately the molecular basis of its elastic behaviour, we studied the thermodynamic properties of module pairs, the smallest structural unit that includes a module-module interface. Thus, selected module pairs and their component single modules from the I-band part of the titin molecule were expressed in Escherichia coli and their heat-induced and denaturant-induced unfolding was investigated with a combination of techniques (circular dichroism, fluorescence spectroscopy and nuclear magnetic resonance). The stabilities of single modules and pairs were determined from denaturation experiments. The module interface was also modelled on the basis of the sequence alignment of all ∼40 immunoglobulin like modules from the I-band and the known structure of one of them. Our results show that all modules and module pairs examined are independently folded in solution. When covalently linked, although weakly interacting, they still behave as autonomous co-operative units upon unfolding. These observations lead us to suggest that folding of titin in vitro is a hierarchical event and that weak interactions between its adjacent modules must only partly account for its presumed elastic function.

AB - The vertebrate striated muscle protein titin is thought to play a critical rôle in myofibril assembly and passive tension. The recently determined complete primary structure of titin revealed a modular architecture that opens the way to a structural characterisation and the understanding of essential properties of this molecule through dissection into units that are structurally and/or functionally relevant. To understand the assembly process of titin, and ultimately the molecular basis of its elastic behaviour, we studied the thermodynamic properties of module pairs, the smallest structural unit that includes a module-module interface. Thus, selected module pairs and their component single modules from the I-band part of the titin molecule were expressed in Escherichia coli and their heat-induced and denaturant-induced unfolding was investigated with a combination of techniques (circular dichroism, fluorescence spectroscopy and nuclear magnetic resonance). The stabilities of single modules and pairs were determined from denaturation experiments. The module interface was also modelled on the basis of the sequence alignment of all ∼40 immunoglobulin like modules from the I-band and the known structure of one of them. Our results show that all modules and module pairs examined are independently folded in solution. When covalently linked, although weakly interacting, they still behave as autonomous co-operative units upon unfolding. These observations lead us to suggest that folding of titin in vitro is a hierarchical event and that weak interactions between its adjacent modules must only partly account for its presumed elastic function.

KW - Connectin

KW - Elasticity

KW - Interface

KW - Module

KW - Muscle

KW - Unfolding

UR - http://www.scopus.com/inward/record.url?scp=0030009318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030009318&partnerID=8YFLogxK

U2 - 10.1006/jmbi.1996.0050

DO - 10.1006/jmbi.1996.0050

M3 - Article

VL - 255

SP - 604

EP - 616

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -