6gzj | pdb_00006gzj

Complex between the dynein light chain DYNLL1/DLC8 and the specific domain of large myelin-associated glycoprotein L-MAG

spinqualitylabelsall models 6gzj, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gzj is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL Gene: DYNLL1, DLC1, DNCL1, DNCLC1, HDLC1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DYL1_HUMAN] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures. Binds and inhibits the catalytic activity of neuronal nitric oxide synthase. Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1. Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity. [MAG_MOUSE] Adhesion molecule in postnatal neural development that mediates sialic-acid dependent cell-cell interactions between neuronal and myelinating cells. Preferentially binds to alpha-2,3-linked sialic acid. Isoform L-MAG is critical for the formation of myelin in the CNS, whereas isoform S-MAG is sufficient to maintain the integrity of myelin in PNS. Publication Abstract from PubMed The close association of myelinated axons and their myelin sheaths involves numerous intercellular molecular interactions. For example, myelin-associated glycoprotein (MAG) mediates myelin-to-axon adhesion and signalling via molecules on the axonal surface. However, knowledge about intracellular binding partners of myelin proteins, including MAG, has remained limited. The two splice isoforms of MAG, S- and L-MAG, display distinct cytoplasmic domains and spatiotemporal expression profiles. We used yeast 2-hybrid screening to identify interaction partners of L-MAG and found the dynein light chain DYNLL1 (also termed DLC8). DYNLL1 homodimers are known to facilitate dimerization of target proteins. L-MAG and DYNLL1 associate with high affinity, as confirmed with recombinant proteins in vitro. Structural analyses of the purified complex indicate that the DYNLL1-binding segment is localized close to the L-MAG C terminus, next to the Fyn kinase Tyr phosphorylation site. The crystal structure of the complex between DYNLL1 and its binding segment on L-MAG shows 2:2 binding in a parallel arrangement, indicating a heterotetrameric complex. The homology between L-MAG and previously characterized DYNLL1-ligands is limited, and some details of binding-site interactions are unique for L-MAG. The structure of the complex between the entire L-MAG cytoplasmic domain and DYNLL1, as well as that of the the extracellular domain of MAG, were modeled based on small-angle X-ray scattering data, allowing structural insights into L-MAG interactions on both membrane surfaces. Our data imply that DYNLL1 dimerizes L-MAG, but not S-MAG, through the formation of a specific 2:2 heterotetramer. This arrangement is likely to affect, in an isoform-specific manner, the functions of MAG in adhesion and myelin-to-axon signalling. This article is protected by copyright. All rights reserved. High-affinity heterotetramer formation between the large myelin-associated glycoprotein and the dynein light chain DYNLL1.,Myllykoski M, Eichel MA, Jung RB, Kelm S, Werner HB, Kursula P J Neurochem. 2018 Sep 27. doi: 10.1111/jnc.14598. PMID:30261098 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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