5vr2

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mouse myocilin leucine zipper C-terminal 7 heptad repeat

Structural highlights

5vr2 is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.922Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MYOC_MOUSE Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling (By similarity). Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling (PubMed:23629661). Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling (PubMed:23897819). Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex (PubMed:22371502). Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork (By similarity).[UniProtKB:Q99972][1] [2] [3]

Publication Abstract from PubMed

Glaucoma-associated myocilin is a member of the olfactomedins, a protein family involved in neuronal development and human diseases. Molecular studies of the myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a Y-shaped parallel dimer-of-dimers with distinct tetramer and dimer regions. The structure of the dimeric C-terminal 7-heptad repeats elucidates an unexpected repeat pattern involving inter-strand stabilization by oppositely charged residues. Molecular dynamics simulations reveal an alternate accessible conformation in which the terminal inter-strand disulfide limits the extent of unfolding and results in a kinked configuration. By inference, full-length myocilin is also branched, with two pairs of C-terminal olfactomedin domains. Selected variants within the N-terminal region alter the apparent quaternary structure of myocilin but do so without compromising stability or causing aggregation. In addition to increasing our structural knowledge of naturally occurring extracellular coiled coils and biomedically important olfactomedins, this work broadens the scope of protein misfolding in the pathogenesis of myocilin-associated glaucoma.

Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of Glaucoma-Associated Myocilin.,Hill SE, Nguyen E, Donegan RK, Patterson-Orazem AC, Hazel A, Gumbart JC, Lieberman RL Structure. 2017 Oct 12. pii: S0969-2126(17)30299-X. doi:, 10.1016/j.str.2017.09.008. PMID:29056483[4]

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

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References

  1. Joe MK, Kee C, Tomarev SI. Myocilin interacts with syntrophins and is member of dystrophin-associated protein complex. J Biol Chem. 2012 Apr 13;287(16):13216-27. doi: 10.1074/jbc.M111.224063. Epub, 2012 Feb 25. PMID:22371502 doi:http://dx.doi.org/10.1074/jbc.M111.224063
  2. Kwon HS, Johnson TV, Tomarev SI. Myocilin stimulates osteogenic differentiation of mesenchymal stem cells through mitogen-activated protein kinase signaling. J Biol Chem. 2013 Jun 7;288(23):16882-94. doi: 10.1074/jbc.M112.422972. Epub 2013, Apr 29. PMID:23629661 doi:http://dx.doi.org/10.1074/jbc.M112.422972
  3. Kwon HS, Johnson TV, Joe MK, Abu-Asab M, Zhang J, Chan CC, Tomarev SI. Myocilin mediates myelination in the peripheral nervous system through ErbB2/3 signaling. J Biol Chem. 2013 Sep 13;288(37):26357-71. doi: 10.1074/jbc.M112.446138. Epub, 2013 Jul 29. PMID:23897819 doi:http://dx.doi.org/10.1074/jbc.M112.446138
  4. Hill SE, Nguyen E, Donegan RK, Patterson-Orazem AC, Hazel A, Gumbart JC, Lieberman RL. Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of Glaucoma-Associated Myocilin. Structure. 2017 Oct 12. pii: S0969-2126(17)30299-X. doi:, 10.1016/j.str.2017.09.008. PMID:29056483 doi:http://dx.doi.org/10.1016/j.str.2017.09.008

Contents


PDB ID 5vr2

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OCA

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