QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 26 October 2004
doi: 10.1242/jcs.01501

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.01501v1 117/24/5781    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nagy, A. Articles by Kellermayer, M. S. Z. Search for Related Content PubMed PubMed Citation Articles by Nagy, A. Articles by Kellermayer, M. S. Z.

Differential actin binding along the PEVK domain of skeletal muscle titin

Attila Nagy¹, Paola Cacciafesta^1,*, László Grama¹, András Kengyel¹, András Málnási-Csizmadia² and Miklós S. Z. Kellermayer^1,

¹ Department of Biophysics, University of Pécs, Faculty of Medicine, Szigeti út 12. Pécs 7624, Hungary
² Department of Biochemistry, Eötvös University, Pázmány Péter sétány 1/c., Budapest 1117, Hungary

Author for correspondence (e-mail: miklos.kellermayer.jr{at}aok.pte.hu)

Accepted 18 August 2004

Parts of the PEVK (Pro-Glu-Val-Lys) domain of the skeletal muscle isoform of the giant intrasarcomeric protein titin have been shown to bind F-actin. However, the mechanisms and physiological function of this are poorly understood. To test for actin binding along PEVK, we expressed contiguous N-terminal (PEVKI), middle (PEVKII), and C-terminal (PEVKIII) PEVK segments of the human soleus muscle isoform. We found a differential actin binding along PEVK in solid-state binding, cross-linking and in vitro motility assays. The order of apparent affinity is PEVKII>PEVKI>PEVKIII. To explore which sequence motifs convey the actin-binding property, we cloned and expressed PEVK fragments with different motif structure: PPAK, polyE-rich and pure polyE fragments. The polyE-containing fragments had a stronger apparent actin binding, suggesting that a local preponderance of polyE motifs conveys an enhanced local actin-binding property to PEVK. The actin binding of PEVK may serve as a viscous bumper mechanism that limits the velocity of unloaded muscle shortening towards short sarcomere lengths. Variations in the motif structure of PEVK might be a method of regulating the magnitude of the viscous drag.

Key words: Titin, PEVK, PPAK, polyE, In vitro motility, Elasticity

This article has been cited by other articles:

				W. A. Linke Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction Cardiovasc Res, March 1, 2008; 77(4): 637 - 648. [Abstract] [Full Text] [PDF]

				P. Bianco, A. Nagy, A. Kengyel, D. Szatmari, Z. Martonfalvi, T. Huber, and M. S. Z. Kellermayer Interaction Forces between F-Actin and Titin PEVK Domain Measured with Optical Tweezers Biophys. J., September 15, 2007; 93(6): 2102 - 2109. [Abstract] [Full Text] [PDF]

				L. Fabian, X. Xia, D. V. Venkitaramani, K. M. Johansen, J. Johansen, D. J. Andrew, and A. Forer Titin in insect spermatocyte spindle fibers associates with microtubules, actin, myosin and the matrix proteins skeletor, megator and chromator J. Cell Sci., July 1, 2007; 120(13): 2190 - 2204. [Abstract] [Full Text] [PDF]

				K. Ono, R. Yu, K. Mohri, and S. Ono Caenorhabditis elegans Kettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle Mol. Biol. Cell, June 1, 2006; 17(6): 2722 - 2734. [Abstract] [Full Text] [PDF]