Calcium-Dependent Molecular Spring Elements in the Giant Protein Titin
Titin (also known as connectin) is a giant protein with a wide range of cellular functions, including providing muscle cells with elasticity. Its physiological extension is largely derived from the PEVK segment, rich in proline (P), glutamate (E), valine (V), and lysine (K) residues. We studied reco...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2003-11, Vol.100 (23), p.13716-13721 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Labeit, Dietmar Watanabe, Kaori Witt, Christian Fujita, Hideaki Wu, Yiming Lahmers, Sunshine Funck, Theodor Labeit, Siegfried Granzier, Henk |
| description | Titin (also known as connectin) is a giant protein with a wide range of cellular functions, including providing muscle cells with elasticity. Its physiological extension is largely derived from the PEVK segment, rich in proline (P), glutamate (E), valine (V), and lysine (K) residues. We studied recombinant PEVK molecules containing the two conserved elements: ≈28-residue PEVK repeats and E-rich motifs. Single molecule experiments revealed that calcium-induced conformational changes reduce the bending rigidity of the PEVK fragments, and site-directed mutagenesis identified four glutamate residues in the E-rich motif that was studied (exon 129), as critical for this process. Experiments with muscle fibers showed that titin-based tension is calcium responsive. We propose that the PEVK segment contains E-rich motifs that render titin a calcium-dependent molecular spring that adapts to the physiological state of the cell. |
| doi_str_mv | 10.1073/pnas.2235652100 |
| format | Article |
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Its physiological extension is largely derived from the PEVK segment, rich in proline (P), glutamate (E), valine (V), and lysine (K) residues. We studied recombinant PEVK molecules containing the two conserved elements: ≈28-residue PEVK repeats and E-rich motifs. Single molecule experiments revealed that calcium-induced conformational changes reduce the bending rigidity of the PEVK fragments, and site-directed mutagenesis identified four glutamate residues in the E-rich motif that was studied (exon 129), as critical for this process. Experiments with muscle fibers showed that titin-based tension is calcium responsive. We propose that the PEVK segment contains E-rich motifs that render titin a calcium-dependent molecular spring that adapts to the physiological state of the cell.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2235652100</identifier><identifier>PMID: 14593205</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Amino Acid Motifs ; Amino Acid Sequence ; Anatomy & physiology ; Biological Sciences ; Calcium ; Calcium - metabolism ; Cantilevers ; Connectin ; Emission spectra ; Exons ; Fluorescence ; Gene Deletion ; Glutamic Acid - chemistry ; Histograms ; Humans ; Lysine - chemistry ; Molecular biology ; Molecular Sequence Data ; Molecules ; Muscle Proteins - chemistry ; Muscles - metabolism ; Mutagenesis, Site-Directed ; Proline - chemistry ; Protein Conformation ; Protein Kinases - chemistry ; Proteins ; Recombinant Proteins - chemistry ; Sarcomeres ; Sequence Homology, Amino Acid ; Spectrometry, Fluorescence ; Ultrasonics ; Valine - chemistry</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2003-11, Vol.100 (23), p.13716-13721</ispartof><rights>Copyright 1993-2003 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 11, 2003</rights><rights>Copyright © 2003, The National Academy of Sciences 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-16d6d53cbcfde6f7cee62ef78d9608aad34dc824f40f86f2209dbda95a9ad8473</citedby><cites>FETCH-LOGICAL-c592t-16d6d53cbcfde6f7cee62ef78d9608aad34dc824f40f86f2209dbda95a9ad8473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/100/23.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3148205$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3148205$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14593205$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Labeit, Dietmar</creatorcontrib><creatorcontrib>Watanabe, Kaori</creatorcontrib><creatorcontrib>Witt, Christian</creatorcontrib><creatorcontrib>Fujita, Hideaki</creatorcontrib><creatorcontrib>Wu, Yiming</creatorcontrib><creatorcontrib>Lahmers, Sunshine</creatorcontrib><creatorcontrib>Funck, Theodor</creatorcontrib><creatorcontrib>Labeit, Siegfried</creatorcontrib><creatorcontrib>Granzier, Henk</creatorcontrib><title>Calcium-Dependent Molecular Spring Elements in the Giant Protein Titin</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Titin (also known as connectin) is a giant protein with a wide range of cellular functions, including providing muscle cells with elasticity. 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We propose that the PEVK segment contains E-rich motifs that render titin a calcium-dependent molecular spring that adapts to the physiological state of the cell.</description><subject>Amino Acid Motifs</subject><subject>Amino Acid Sequence</subject><subject>Anatomy & physiology</subject><subject>Biological Sciences</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Cantilevers</subject><subject>Connectin</subject><subject>Emission spectra</subject><subject>Exons</subject><subject>Fluorescence</subject><subject>Gene Deletion</subject><subject>Glutamic Acid - chemistry</subject><subject>Histograms</subject><subject>Humans</subject><subject>Lysine - chemistry</subject><subject>Molecular biology</subject><subject>Molecular Sequence Data</subject><subject>Molecules</subject><subject>Muscle Proteins - chemistry</subject><subject>Muscles - metabolism</subject><subject>Mutagenesis, Site-Directed</subject><subject>Proline - chemistry</subject><subject>Protein Conformation</subject><subject>Protein Kinases - chemistry</subject><subject>Proteins</subject><subject>Recombinant Proteins - chemistry</subject><subject>Sarcomeres</subject><subject>Sequence Homology, Amino Acid</subject><subject>Spectrometry, Fluorescence</subject><subject>Ultrasonics</subject><subject>Valine - chemistry</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0c9rFDEUB_Agil2rZy8igwfBw7QvPyc5eJC1rUJFwXoO2STTzpLJrElG9L83wy5d9eIpkPd5L9_wEHqO4QxDR8930eQzQigXnGCAB2iFQeFWMAUP0QqAdK1khJ2gJzlvAUBxCY_RCWZcUQJ8hS7XJthhHtv3fuej87E0n6bg7RxMar7u0hBvm4vgx1rIzRCbcuebq8FU9iVNxdebm6EM8Sl61JuQ_bPDeYq-XV7crD-015-vPq7fXbeWK1JaLJxwnNqN7Z0XfWe9F8T3nXRKgDTGUeasJKxn0EvREwLKbZxR3CjjJOvoKXq7n7ubN6N3tsZKJuiaczTpl57MoP-uxOFO304_NBFUdqr2vz70p-n77HPR45CtD8FEP81ZY0W47PACX_0Dt9OcYv2bJoAZo0AXdL5HNk05J9_fB8Ggl_3oZT_6uJ_a8fLP_Ed_WEgFzQEsncdxoAnVmHZYVPLmP0T3cwjF_yzVvtjbbS5TuscUM7m89htA167p</recordid><startdate>20031111</startdate><enddate>20031111</enddate><creator>Labeit, Dietmar</creator><creator>Watanabe, Kaori</creator><creator>Witt, Christian</creator><creator>Fujita, Hideaki</creator><creator>Wu, Yiming</creator><creator>Lahmers, Sunshine</creator><creator>Funck, Theodor</creator><creator>Labeit, Siegfried</creator><creator>Granzier, Henk</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20031111</creationdate><title>Calcium-Dependent Molecular Spring Elements in the Giant Protein Titin</title><author>Labeit, Dietmar ; 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| subjects | Amino Acid Motifs Amino Acid Sequence Anatomy & physiology Biological Sciences Calcium Calcium - metabolism Cantilevers Connectin Emission spectra Exons Fluorescence Gene Deletion Glutamic Acid - chemistry Histograms Humans Lysine - chemistry Molecular biology Molecular Sequence Data Molecules Muscle Proteins - chemistry Muscles - metabolism Mutagenesis, Site-Directed Proline - chemistry Protein Conformation Protein Kinases - chemistry Proteins Recombinant Proteins - chemistry Sarcomeres Sequence Homology, Amino Acid Spectrometry, Fluorescence Ultrasonics Valine - chemistry |
| title | Calcium-Dependent Molecular Spring Elements in the Giant Protein Titin |
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