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From the same journal

Association of the Chaperone B-crystallin with Titin in Heart Muscle

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Published copy (DOI)

Author(s)

  • Belinda Bullard
  • Charles Ferguson
  • Ave Minajeva
  • Mark C. Leake
  • Mathias Gautel
  • Dietmar Labeit
  • Linlin Ding
  • Siegfried Labeit
  • Joseph Horwitz
  • Kevin R. Leonard
  • Wolfgang A. Linke

Department/unit(s)

Publication details

JournalThe Journal of biological chemistry
DateE-pub ahead of print - 4 Dec 2003
DatePublished (current) - 27 Feb 2004
Issue number9
Volume279
Number of pages8
Pages (from-to)7917-7924
Early online date4/12/03
Original languageEnglish

Abstract

alphaB-crystallin, a major component of the vertebrate lens, is a chaperone belonging to the family of small heat shock proteins. These proteins form oligomers that bind to partially unfolded substrates and prevent denaturation. alphaB-crystallin in cardiac muscle binds to myofibrils under conditions of ischemia, and previous work has shown that the protein binds to titin in the I-band of cardiac fibers (Golenhofen, N., Arbeiter, A., Koob, R., and Drenckhahn, D. (2002) J. Mol. Cell. Cardiol. 34, 309-319). This part of titin extends as muscles are stretched and is made up of immunoglobulin-like modules and two extensible regions (N2B and PEVK) that have no well defined secondary structure. We have followed the position of alphaB-crystallin in stretched cardiac fibers relative to a known part of the titin sequence. alphaB-crystallin bound to a discrete region of the I-band that moved away from the Z-disc as sarcomeres were extended. In the physiological range of sarcomere lengths, alphaB-crystallin bound in the position of the N2B region of titin, but not to PEVK. In overstretched myofibrils, it was also in the Ig region between N2B and the Z-disc. Binding between alphaB-crystallin and N2B was confirmed using recombinant titin fragments. The Ig domains in an eight-domain fragment were stabilized by alphaB-crystallin; atomic force microscopy showed that higher stretching forces were needed to unfold the domains in the presence of the chaperone. Reversible association with alphaB-crystallin would protect I-band titin from stress liable to cause domain unfolding until conditions are favorable for refolding to the native state.

    Research areas

  • Animals, Binding Sites, Circular Dichroism, Connectin, Drug Stability, Electrophoresis, Polyacrylamide Gel, Humans, Immunoglobulins, Microscopy, Fluorescence, Microscopy, Immunoelectron, Muscle Proteins, Myocardium, Myofibrils, Peptide Fragments, Protein Folding, Protein Kinases, Rabbits, Recombinant Proteins, Sarcomeres, alpha-Crystallin B Chain

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