title: Structural mechanism of the dynein power stroke.
abstract: Dyneins are large microtubule motor proteins required for mitosis, intracellular transport and ciliary and flagellar motility. They generate force through a power-stroke mechanism, which is an ATP-consuming cycle of pre- and post-power-stroke conformational changes that cause relative motion between different dynein domains. However, key structural details of dynein's force generation remain elusive. Here, using cryo-electron tomography of intact, active (that is, beating), rapidly frozen sea urchin sperm flagella, we determined the in situ three-dimensional structures of all domains of both pre- and post-power-stroke dynein, including the previously unresolved linker and stalk of pre-power-stroke dynein. Our results reveal that the rotation of the head relative to the linker is the key action in dynein movement, and that there are at least two distinct pre-power-stroke conformations: pre-I (microtubule-detached) and pre-II (microtubule-bound). We provide three-dimensional reconstructions of native dyneins in three conformational states, in situ, allowing us to propose a molecular model of the structural cycle underlying dynein movement.
authors.affiliation: Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham Massachusetts 02454-9110, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham Massachusetts 02454-9110, USA.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Okada
authors.affiliation: Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham Massachusetts 02454-9110, USA.
authors.forename: Milen
authors.initials: M
authors.lastname: Raytchev
authors.affiliation: Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham Massachusetts 02454-9110, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham Massachusetts 02454-9110, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Nicastro
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D004734:Energy Metabolism; D005407:Flagella / Q000378:metabolism* / Q000648:ultrastructure; D006868:Hydrolysis; D008297:Male; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D012617:Sea Urchins / Q000378:metabolism* / Q000648:ultrastructure; D013094:Spermatozoa / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000255:Adenosine Triphosphate; D004398:Dyneins
references.citation: J Cell Sci. 2006 Nov 1;119(Pt 21):4369-71
references.pmid: 17074830
references.citation: Biochim Biophys Acta. 2012 Jan;1823(1):182-91
references.pmid: 22062687
references.citation: J Struct Biol. 2005 Oct;152(1):36-51
references.pmid: 16182563
references.citation: Nat Struct Mol Biol. 2012 Jan 08;19(2):193-200
references.pmid: 22231401
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19702-7
references.pmid: 19064920
references.citation: Nature. 2003 Feb 13;421(6924):715-8
references.pmid: 12610617
references.citation: Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93
references.pmid: 17955020
references.citation: Structure. 2012 Oct 10;20(10):1670-80
references.pmid: 22863569
references.citation: Pharmacol Ther. 2011 Jun;130(3):348-63
references.pmid: 21420428
references.citation: J Chem Phys. 2009 Jan 14;130(2):025101
references.pmid: 19154055
references.citation: Symp Soc Exp Biol. 1982;35:225-87
references.pmid: 6764041
references.citation: J Cell Biol. 2009 Dec 14;187(6):921-33
references.pmid: 20008568
references.citation: J Comput Chem. 2004 Oct;25(13):1605-12
references.pmid: 15264254
references.citation: Nature. 2012 Mar 07;484(7394):345-50
references.pmid: 22398446
references.citation: PLoS One. 2012;7(10):e46494
references.pmid: 23071579
references.citation: Proc Natl Acad Sci U S A. 1981 Feb;78(2):1033-6
references.pmid: 6453342
references.citation: J Struct Biol. 2011 Sep;175(3):288-99
references.pmid: 21616153
references.citation: Nature. 1999 Aug 5;400(6744):586-90
references.pmid: 10448863
references.citation: Cell. 2009 Feb 6;136(3):485-95
references.pmid: 19203583
references.citation: Cell Motil Cytoskeleton. 2007 Jul;64(7):489-95
references.pmid: 17366641
references.citation: Nat Struct Mol Biol. 2009 Mar;16(3):325-33
references.pmid: 19198589
references.citation: Science. 2006 Aug 18;313(5789):944-8
references.pmid: 16917055
references.citation: Cell. 2012 Aug 31;150(5):975-86
references.pmid: 22939623
references.citation: J Mol Biol. 2012 Sep 14;422(2):163-80
references.pmid: 22683354
references.citation: Nature. 2004 Feb 12;427(6975):649-52
references.pmid: 14961123
references.citation: Mol Biol Cell. 2012 Sep;23(18):3554-65
references.pmid: 22855525
references.citation: Biochim Biophys Acta. 2000 Mar 17;1496(1):60-75
references.pmid: 10722877
references.citation: Proc Natl Acad Sci U S A. 1971 Dec;68(12):3092-6
references.pmid: 5289252
references.citation: Science. 2008 Dec 12;322(5908):1691-5
references.pmid: 19074350
references.citation: J Cell Biol. 1972 Sep;54(3):507-39
references.pmid: 4558009
references.citation: J Struct Biol. 2012 Aug;179(2):222-8
references.pmid: 22406539
references.citation: Annu Rev Biophys Biophys Chem. 1985;14:161-88
references.pmid: 3159394
references.citation: Nat Struct Mol Biol. 2010 Jun;17(6):761-7
references.pmid: 20453857
references.citation: Nat Protoc. 2006;1(6):2813-9
references.pmid: 17406539
references.citation: Science. 1965 Jul 23;149(3682):424-6
references.pmid: 17809406
references.citation: Science. 2004 Jan 30;303(5658):676-8
references.pmid: 14684828
references.citation: J Cell Biol. 1992 Sep;118(5):1189-200
references.pmid: 1387406
references.citation: Nat Struct Mol Biol. 2012 Mar 14;19(5):492-7, S1
references.pmid: 22426545
references.citation: J Struct Biol. 1996 Jan-Feb;116(1):71-6
references.pmid: 8742726