Proteopedia

5i4e

Crystal Structure of Human Nonmuscle Myosin 2C motor domainCrystal Structure of Human Nonmuscle Myosin 2C motor domain

Structural highlights

5i4e is a 1 chain structure with sequence from Dictyostelium discoideum and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.25Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MYH14_HUMAN Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome;Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

ACTNA_DICDI F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Increases the actin-stimulated ATPase activity of myosin. Involved in vegetative cell growth, phagocytosis, motility and development, probably through stabilization of the actin network in the cortical cytoskeleton.[1] [2] [3] [4] [5] [6] [7] [8] MYH14_HUMAN Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.

Publication Abstract from PubMed

Despite a generic, highly conserved motor domain, ATP turnover kinetics and their activation by F-actin vary greatly between myosin-2 isoforms. Here, we present a 2.25 A pre-powerstroke state (ADPVO4) crystal structure of the human nonmuscle myosin-2C motor domain, one of the slowest myosins characterized. In combination with integrated mutagenesis, ensemble-solution kinetics, and molecular dynamics simulation approaches, the structure reveals an allosteric communication pathway that connects the distal end of the motor domain with the active site. Disruption of this pathway by mutation of hub residue R788, which forms the center of a cluster of interactions connecting the converter, the SH1-SH2 helix, the relay helix, and the lever, abolishes nonmuscle myosin-2 specific kinetic signatures. Our results provide insights into structural changes in the myosin motor domain that are triggered upon F-actin binding and contribute critically to the mechanochemical behavior of stress fibers, actin arcs, and cortical actin-based structures.

Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C.,Chinthalapudi K, Heissler SM, Preller M, Sellers JR, Manstein DJ Elife. 2017 Dec 19;6. pii: 32742. doi: 10.7554/eLife.32742. PMID:29256864[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Weber I. Computer-assisted morphometry of cell-substratum contacts. Croat Med J. 1999 Sep;40(3):334-9. PMID:10411959
  2. ↑ Rivero F, Furukawa R, Fechheimer M, Noegel AA. Three actin cross-linking proteins, the 34 kDa actin-bundling protein, alpha-actinin and gelation factor (ABP-120), have both unique and redundant roles in the growth and development of Dictyostelium. J Cell Sci. 1999 Aug;112 ( Pt 16):2737-51. PMID:10413681
  3. ↑ Ponte E, Rivero F, Fechheimer M, Noegel A, Bozzaro S. Severe developmental defects in Dictyostelium null mutants for actin-binding proteins. Mech Dev. 2000 Mar 1;91(1-2):153-61. doi: 10.1016/s0925-4773(99)00292-0. PMID:10704840 doi:http://dx.doi.org/10.1016/s0925-4773(99)00292-0
  4. ↑ Witke W, Schleicher M, Noegel AA. Redundancy in the microfilament system: abnormal development of Dictyostelium cells lacking two F-actin cross-linking proteins. Cell. 1992 Jan 10;68(1):53-62. PMID:1732064
  5. ↑ Wallraff E, Schleicher M, Modersitzki M, Rieger D, Isenberg G, Gerisch G. Selection of Dictyostelium mutants defective in cytoskeletal proteins: use of an antibody that binds to the ends of alpha-actinin rods. EMBO J. 1986 Jan;5(1):61-7. PMID:3956480
  6. ↑ Condeelis J, Vahey M, Carboni JM, DeMey J, Ogihara S. Properties of the 120,000- and 95,000-dalton actin-binding proteins from Dictyostelium discoideum and their possible functions in assembling the cytoplasmic matrix. J Cell Biol. 1984 Jul;99(1 Pt 2):119s-126s. PMID:6746725
  7. ↑ Witke W, Hofmann A, Koppel B, Schleicher M, Noegel AA. The Ca(2+)-binding domains in non-muscle type alpha-actinin: biochemical and genetic analysis. J Cell Biol. 1993 May;121(3):599-606. PMID:8486739
  8. ↑ Rivero F, Koppel B, Peracino B, Bozzaro S, Siegert F, Weijer CJ, Schleicher M, Albrecht R, Noegel AA. The role of the cortical cytoskeleton: F-actin crosslinking proteins protect against osmotic stress, ensure cell size, cell shape and motility, and contribute to phagocytosis and development. J Cell Sci. 1996 Nov;109 ( Pt 11):2679-91. PMID:8937986
  9. ↑ Chinthalapudi K, Heissler SM, Preller M, Sellers JR, Manstein DJ. Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C. Elife. 2017 Dec 19;6. pii: 32742. doi: 10.7554/eLife.32742. PMID:29256864 doi:http://dx.doi.org/10.7554/eLife.32742

5i4e, resolution 2.25Å

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