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rdf:type |
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lifeskim:mentions |
umls-concept:C1149666,
umls-concept:C1180334,
umls-concept:C1514562,
umls-concept:C1514721,
umls-concept:C1707271,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1947953,
umls-concept:C2587213,
umls-concept:C2700372
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pubmed:issue |
38
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pubmed:dateCreated |
2005-9-19
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pubmed:abstractText |
The dynein motor domain consists of a ring of six AAA domains with a protruding microtubule-binding stalk and a C-terminal domain of unknown function. To understand how conformational information is communicated within this complex structure, we produced a series of recombinant and proteolytic rat motor domain fragments, which we analyzed enzymatically. A recombinant 210-kDa half-motor domain fragment surprisingly exhibited a 6-fold higher steady state ATPase activity than a 380-kDa complete motor domain fragment. The increased ATPase activity was associated with a complete loss of sensitivity to inhibition by vanadate and an approximately 100-fold increase in the rate of ADP release. The time course of product release was discovered to be biphasic, and each phase was stimulated approximately 1000-fold by microtubule binding to the 380-kDa motor domain. Both the half-motor and full motor domain fragments were remarkably resistant to tryptic proteolysis, exhibiting either two or three major cleavage sites. Cleavage near the C terminus of the 380-kDa motor domain released a 32-kDa fragment and abolished sensitivity to vanadate. Cleavage at this site was insensitive to ATP or 5'-adenylyl-beta,gamma-imidodiphosphate but was blocked by ADP-AlF3 or ADP-vanadate. Based on these data, we proposed a model for long range allosteric control of product release at AAA1 and AAA3 through the microtubule-binding stalk and the C-terminal domain, the latter of which may interact with AAA1 to close the motor domain ring in a cross-bridge cycle-dependent manner.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Aluminum Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Diphosphonates,
http://linkedlifedata.com/resource/pubmed/chemical/Dyneins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorides,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Solvents,
http://linkedlifedata.com/resource/pubmed/chemical/Trypsin,
http://linkedlifedata.com/resource/pubmed/chemical/Vanadates,
http://linkedlifedata.com/resource/pubmed/chemical/aluminum fluoride,
http://linkedlifedata.com/resource/pubmed/chemical/imidodiphosphonic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33045-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16030013-Adenosine Diphosphate,
pubmed-meshheading:16030013-Adenosine Triphosphatases,
pubmed-meshheading:16030013-Adenosine Triphosphate,
pubmed-meshheading:16030013-Allosteric Site,
pubmed-meshheading:16030013-Aluminum Compounds,
pubmed-meshheading:16030013-Animals,
pubmed-meshheading:16030013-Chromatography, Ion Exchange,
pubmed-meshheading:16030013-Cytoplasm,
pubmed-meshheading:16030013-Diphosphonates,
pubmed-meshheading:16030013-Dose-Response Relationship, Drug,
pubmed-meshheading:16030013-Dyneins,
pubmed-meshheading:16030013-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:16030013-Fluorides,
pubmed-meshheading:16030013-Hydrolysis,
pubmed-meshheading:16030013-Kinetics,
pubmed-meshheading:16030013-Microtubules,
pubmed-meshheading:16030013-Models, Biological,
pubmed-meshheading:16030013-Models, Statistical,
pubmed-meshheading:16030013-Protein Conformation,
pubmed-meshheading:16030013-Protein Structure, Tertiary,
pubmed-meshheading:16030013-Rats,
pubmed-meshheading:16030013-Recombinant Proteins,
pubmed-meshheading:16030013-Solvents,
pubmed-meshheading:16030013-Trypsin,
pubmed-meshheading:16030013-Ultraviolet Rays,
pubmed-meshheading:16030013-Vanadates
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pubmed:year |
2005
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pubmed:articleTitle |
Long range allosteric control of cytoplasmic dynein ATPase activity by the stalk and C-terminal domains.
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pubmed:affiliation |
Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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