Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin
The highly oriented filamentous protein network of muscle constantly experiences significant mechanical load during muscle operation. The dimeric protein myomesin has been identified as an important M-band component supporting the mechanical integrity of the entire sarcomere. Recent structural studi...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2011-08, Vol.108 (34), p.14139-14144 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Berkemeier, Felix Bertz, Morten Xiao, Senbo Pinotsis, Nikos Wilmanns, Matthias Gräter, Frauke Rief, Matthias |
| description | The highly oriented filamentous protein network of muscle constantly experiences significant mechanical load during muscle operation. The dimeric protein myomesin has been identified as an important M-band component supporting the mechanical integrity of the entire sarcomere. Recent structural studies have revealed a long α-helical linker between the C-terminal immunoglobulin (Ig) domains My12 and My13 of myomesin. In this paper, we have used single-molecule force spectroscopy in combination with molecular dynamics simulations to characterize the mechanics of the myomesin dimer comprising immunoglobulin domains My12–My13. We find that at forces of approximately 30 pN the a-helical linker reversibly elongates allowing the molecule to extend by more than the folded extension of a full domain. High-resolution measurements directly reveal the equilibrium folding/unfolding kinetics of the individual helix. We show that α-helix unfolding mechanically protects the molecule homodimerization from dissociation at physiologically relevant forces. As fast and reversible molecular springs the myomesin α-helical linkers are an essential component for the structural integrity of the M band. |
| doi_str_mv | 10.1073/pnas.1105734108 |
| format | Article |
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The dimeric protein myomesin has been identified as an important M-band component supporting the mechanical integrity of the entire sarcomere. Recent structural studies have revealed a long α-helical linker between the C-terminal immunoglobulin (Ig) domains My12 and My13 of myomesin. In this paper, we have used single-molecule force spectroscopy in combination with molecular dynamics simulations to characterize the mechanics of the myomesin dimer comprising immunoglobulin domains My12–My13. We find that at forces of approximately 30 pN the a-helical linker reversibly elongates allowing the molecule to extend by more than the folded extension of a full domain. High-resolution measurements directly reveal the equilibrium folding/unfolding kinetics of the individual helix. We show that α-helix unfolding mechanically protects the molecule homodimerization from dissociation at physiologically relevant forces. As fast and reversible molecular springs the myomesin α-helical linkers are an essential component for the structural integrity of the M band.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1105734108</identifier><identifier>PMID: 21825161</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Biological Sciences ; Biomechanical Phenomena ; Connectin ; Dimerization ; Dimers ; dissociation ; Free energy ; Immunoglobulins ; Kinetics ; mechanical loads ; Microscopy, Atomic Force ; molecular dynamics ; Molecular Dynamics Simulation ; Molecules ; muscle protein ; Muscle Proteins - chemistry ; Muscle Proteins - metabolism ; Protein Folding ; Protein isoforms ; Protein Multimerization ; Protein Stability ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Unfolding ; Proteins ; Sarcomeres ; Spectroscopy ; Sprains and strains</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2011-08, Vol.108 (34), p.14139-14144</ispartof><rights>copyright © 1993–2008 National Academy of Sciences of the United States of America</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-8e12ecbbcc35d62f8b701ef28e06d6de07a98935c8bbfe73a5428c1752c5ae73</citedby><cites>FETCH-LOGICAL-c472t-8e12ecbbcc35d62f8b701ef28e06d6de07a98935c8bbfe73a5428c1752c5ae73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/108/34.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27979474$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27979474$$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/21825161$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berkemeier, Felix</creatorcontrib><creatorcontrib>Bertz, Morten</creatorcontrib><creatorcontrib>Xiao, Senbo</creatorcontrib><creatorcontrib>Pinotsis, Nikos</creatorcontrib><creatorcontrib>Wilmanns, Matthias</creatorcontrib><creatorcontrib>Gräter, Frauke</creatorcontrib><creatorcontrib>Rief, Matthias</creatorcontrib><title>Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The highly oriented filamentous protein network of muscle constantly experiences significant mechanical load during muscle operation. The dimeric protein myomesin has been identified as an important M-band component supporting the mechanical integrity of the entire sarcomere. Recent structural studies have revealed a long α-helical linker between the C-terminal immunoglobulin (Ig) domains My12 and My13 of myomesin. In this paper, we have used single-molecule force spectroscopy in combination with molecular dynamics simulations to characterize the mechanics of the myomesin dimer comprising immunoglobulin domains My12–My13. We find that at forces of approximately 30 pN the a-helical linker reversibly elongates allowing the molecule to extend by more than the folded extension of a full domain. High-resolution measurements directly reveal the equilibrium folding/unfolding kinetics of the individual helix. We show that α-helix unfolding mechanically protects the molecule homodimerization from dissociation at physiologically relevant forces. As fast and reversible molecular springs the myomesin α-helical linkers are an essential component for the structural integrity of the M band.</description><subject>Biological Sciences</subject><subject>Biomechanical Phenomena</subject><subject>Connectin</subject><subject>Dimerization</subject><subject>Dimers</subject><subject>dissociation</subject><subject>Free energy</subject><subject>Immunoglobulins</subject><subject>Kinetics</subject><subject>mechanical loads</subject><subject>Microscopy, Atomic Force</subject><subject>molecular dynamics</subject><subject>Molecular Dynamics Simulation</subject><subject>Molecules</subject><subject>muscle protein</subject><subject>Muscle Proteins - chemistry</subject><subject>Muscle Proteins - metabolism</subject><subject>Protein Folding</subject><subject>Protein isoforms</subject><subject>Protein Multimerization</subject><subject>Protein Stability</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Protein Unfolding</subject><subject>Proteins</subject><subject>Sarcomeres</subject><subject>Spectroscopy</subject><subject>Sprains and strains</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQxi0EokvhzAmUG1zSevwnti9IqGoBqRKXcrZsZ9J1lcSLna3Ux-JFeKZ6tUsXLpxGM_ObT9_oI-Qt0DOgip9vZlfOAKhUXADVz8gKqIG2E4Y-JytKmWq1YOKEvCrljlJqpKYvyQkDzSR0sCI_rlxZ2iGNfZxvm9-_2jWOMWBpXGky3mMu0Y_YlCW7ODfOl5R9HTa1WdbYTNsS6nqT04J1ND2kCUucX5MXgxsLvjnUU3JzdXlz8bW9_v7l28Xn6zYIxZZWIzAM3ofAZd-xQXtFAQemkXZ91yNVzmjDZdDeD6i4k4LpAEqyIF3tT8mnvexm6yfsA87V5mg3OU4uP9jkov13M8e1vU33ltffJYMq8OEgkNPPLZbFTrEEHEc3Y9oWq7U0AELKSn78L8mM7gyvOK_o-R4NOZWScXgyBNTuUrO71OwxtXrx_u8_nvg_MVWgOQC7y6OctlxYEMBNRd7tkbuypHyUUEYZoQR_BNfeqjg</recordid><startdate>20110823</startdate><enddate>20110823</enddate><creator>Berkemeier, Felix</creator><creator>Bertz, Morten</creator><creator>Xiao, Senbo</creator><creator>Pinotsis, Nikos</creator><creator>Wilmanns, Matthias</creator><creator>Gräter, Frauke</creator><creator>Rief, Matthias</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>7S9</scope><scope>L.6</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110823</creationdate><title>Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin</title><author>Berkemeier, Felix ; Bertz, Morten ; Xiao, Senbo ; Pinotsis, Nikos ; Wilmanns, Matthias ; Gräter, Frauke ; Rief, Matthias</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-8e12ecbbcc35d62f8b701ef28e06d6de07a98935c8bbfe73a5428c1752c5ae73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biological Sciences</topic><topic>Biomechanical Phenomena</topic><topic>Connectin</topic><topic>Dimerization</topic><topic>Dimers</topic><topic>dissociation</topic><topic>Free energy</topic><topic>Immunoglobulins</topic><topic>Kinetics</topic><topic>mechanical loads</topic><topic>Microscopy, Atomic Force</topic><topic>molecular dynamics</topic><topic>Molecular Dynamics Simulation</topic><topic>Molecules</topic><topic>muscle protein</topic><topic>Muscle Proteins - chemistry</topic><topic>Muscle Proteins - metabolism</topic><topic>Protein Folding</topic><topic>Protein isoforms</topic><topic>Protein Multimerization</topic><topic>Protein Stability</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Protein Unfolding</topic><topic>Proteins</topic><topic>Sarcomeres</topic><topic>Spectroscopy</topic><topic>Sprains and strains</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berkemeier, Felix</creatorcontrib><creatorcontrib>Bertz, Morten</creatorcontrib><creatorcontrib>Xiao, Senbo</creatorcontrib><creatorcontrib>Pinotsis, Nikos</creatorcontrib><creatorcontrib>Wilmanns, Matthias</creatorcontrib><creatorcontrib>Gräter, Frauke</creatorcontrib><creatorcontrib>Rief, Matthias</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Berkemeier, Felix</au><au>Bertz, Morten</au><au>Xiao, Senbo</au><au>Pinotsis, Nikos</au><au>Wilmanns, Matthias</au><au>Gräter, Frauke</au><au>Rief, Matthias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2011-08-23</date><risdate>2011</risdate><volume>108</volume><issue>34</issue><spage>14139</spage><epage>14144</epage><pages>14139-14144</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The highly oriented filamentous protein network of muscle constantly experiences significant mechanical load during muscle operation. The dimeric protein myomesin has been identified as an important M-band component supporting the mechanical integrity of the entire sarcomere. Recent structural studies have revealed a long α-helical linker between the C-terminal immunoglobulin (Ig) domains My12 and My13 of myomesin. In this paper, we have used single-molecule force spectroscopy in combination with molecular dynamics simulations to characterize the mechanics of the myomesin dimer comprising immunoglobulin domains My12–My13. We find that at forces of approximately 30 pN the a-helical linker reversibly elongates allowing the molecule to extend by more than the folded extension of a full domain. High-resolution measurements directly reveal the equilibrium folding/unfolding kinetics of the individual helix. We show that α-helix unfolding mechanically protects the molecule homodimerization from dissociation at physiologically relevant forces. 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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Biological Sciences Biomechanical Phenomena Connectin Dimerization Dimers dissociation Free energy Immunoglobulins Kinetics mechanical loads Microscopy, Atomic Force molecular dynamics Molecular Dynamics Simulation Molecules muscle protein Muscle Proteins - chemistry Muscle Proteins - metabolism Protein Folding Protein isoforms Protein Multimerization Protein Stability Protein Structure, Secondary Protein Structure, Tertiary Protein Unfolding Proteins Sarcomeres Spectroscopy Sprains and strains |
| title | Fast-folding α-helices as reversible strain absorbers in the muscle protein myomesin |
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