Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK
MCAK is a mitotic kinesin that binds to and slides along microtubules (MT) to reach their ends, where MCAK disassembles MTs into tubulin dimers. Now the kinetics of MCAK-MT interaction are directly observed in a single-molecule setup, dissecting the contributions of different MCAK regions to on-rate...
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| Veröffentlicht in: | Nature structural & molecular biology 2010-01, Vol.17 (1), p.77-82 |
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| creator | Cooper, Jeremy R Wagenbach, Michael Asbury, Charles L Wordeman, Linda |
| description | MCAK is a mitotic kinesin that binds to and slides along microtubules (MT) to reach their ends, where MCAK disassembles MTs into tubulin dimers. Now the kinetics of MCAK-MT interaction are directly observed in a single-molecule setup, dissecting the contributions of different MCAK regions to on-rates and tubulin disassembly activity.
The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells. We have functionally dissected the structural features responsible for MCAK's potent microtubule depolymerization activity. MCAK's positively charged neck enhances its delivery to microtubule ends not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK's ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK's ability to remove tubulin subunits. The reported kinetics for these events predicts a nonspecific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule-binding proteins. |
| doi_str_mv | 10.1038/nsmb.1728 |
| format | Article |
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The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells. We have functionally dissected the structural features responsible for MCAK's potent microtubule depolymerization activity. MCAK's positively charged neck enhances its delivery to microtubule ends not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK's ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK's ability to remove tubulin subunits. The reported kinetics for these events predicts a nonspecific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule-binding proteins.</description><identifier>ISSN: 1545-9993</identifier><identifier>EISSN: 1545-9985</identifier><identifier>DOI: 10.1038/nsmb.1728</identifier><identifier>PMID: 19966798</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animals ; Biochemistry ; Biological Microscopy ; Biomedical and Life Sciences ; Catalysis ; Cricetinae ; Cricetulus ; Dimerization ; Eukaryotes ; Image Processing, Computer-Assisted ; Kinesin ; Kinesin - genetics ; Kinesin - metabolism ; Kinetics ; Life Sciences ; Membrane Biology ; Microscopy, Fluorescence ; Microtubules ; Microtubules - metabolism ; Mutation - genetics ; Parameter estimation ; Photobleaching ; Physiological aspects ; Polymerization ; Properties ; Protein Binding ; Protein Structure ; Protein Structure, Tertiary ; Proteins ; Tubulin - metabolism</subject><ispartof>Nature structural & molecular biology, 2010-01, Vol.17 (1), p.77-82</ispartof><rights>Springer Nature America, Inc. 2009</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-2835ed7513df27845e8b9737b9e533df9310a5aa8d500a8ca5f92d9b35262b2c3</citedby><cites>FETCH-LOGICAL-c603t-2835ed7513df27845e8b9737b9e533df9310a5aa8d500a8ca5f92d9b35262b2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nsmb.1728$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nsmb.1728$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19966798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cooper, Jeremy R</creatorcontrib><creatorcontrib>Wagenbach, Michael</creatorcontrib><creatorcontrib>Asbury, Charles L</creatorcontrib><creatorcontrib>Wordeman, Linda</creatorcontrib><title>Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK</title><title>Nature structural & molecular biology</title><addtitle>Nat Struct Mol Biol</addtitle><addtitle>Nat Struct Mol Biol</addtitle><description>MCAK is a mitotic kinesin that binds to and slides along microtubules (MT) to reach their ends, where MCAK disassembles MTs into tubulin dimers. Now the kinetics of MCAK-MT interaction are directly observed in a single-molecule setup, dissecting the contributions of different MCAK regions to on-rates and tubulin disassembly activity.
The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells. We have functionally dissected the structural features responsible for MCAK's potent microtubule depolymerization activity. MCAK's positively charged neck enhances its delivery to microtubule ends not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK's ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK's ability to remove tubulin subunits. The reported kinetics for these events predicts a nonspecific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule-binding proteins.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological Microscopy</subject><subject>Biomedical and Life Sciences</subject><subject>Catalysis</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Dimerization</subject><subject>Eukaryotes</subject><subject>Image Processing, Computer-Assisted</subject><subject>Kinesin</subject><subject>Kinesin - genetics</subject><subject>Kinesin - metabolism</subject><subject>Kinetics</subject><subject>Life Sciences</subject><subject>Membrane Biology</subject><subject>Microscopy, Fluorescence</subject><subject>Microtubules</subject><subject>Microtubules - metabolism</subject><subject>Mutation - genetics</subject><subject>Parameter estimation</subject><subject>Photobleaching</subject><subject>Physiological aspects</subject><subject>Polymerization</subject><subject>Properties</subject><subject>Protein Binding</subject><subject>Protein Structure</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Tubulin - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature structural & molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cooper, Jeremy R</au><au>Wagenbach, Michael</au><au>Asbury, Charles L</au><au>Wordeman, Linda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK</atitle><jtitle>Nature structural & molecular biology</jtitle><stitle>Nat Struct Mol Biol</stitle><addtitle>Nat Struct Mol Biol</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>17</volume><issue>1</issue><spage>77</spage><epage>82</epage><pages>77-82</pages><issn>1545-9993</issn><eissn>1545-9985</eissn><abstract>MCAK is a mitotic kinesin that binds to and slides along microtubules (MT) to reach their ends, where MCAK disassembles MTs into tubulin dimers. Now the kinetics of MCAK-MT interaction are directly observed in a single-molecule setup, dissecting the contributions of different MCAK regions to on-rates and tubulin disassembly activity.
The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells. We have functionally dissected the structural features responsible for MCAK's potent microtubule depolymerization activity. MCAK's positively charged neck enhances its delivery to microtubule ends not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK's ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK's ability to remove tubulin subunits. The reported kinetics for these events predicts a nonspecific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule-binding proteins.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>19966798</pmid><doi>10.1038/nsmb.1728</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biochemistry Biological Microscopy Biomedical and Life Sciences Catalysis Cricetinae Cricetulus Dimerization Eukaryotes Image Processing, Computer-Assisted Kinesin Kinesin - genetics Kinesin - metabolism Kinetics Life Sciences Membrane Biology Microscopy, Fluorescence Microtubules Microtubules - metabolism Mutation - genetics Parameter estimation Photobleaching Physiological aspects Polymerization Properties Protein Binding Protein Structure Protein Structure, Tertiary Proteins Tubulin - metabolism |
| title | Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK |
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