View source for 6ofp


==Structure of the C-terminal cargo binding domain of human Bicaudal D2==
<StructureSection load='6ofp' size='340' side='right'caption='[[6ofp]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ofp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OFP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.006&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ofp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofp OCA], [https://pdbe.org/6ofp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ofp RCSB], [https://www.ebi.ac.uk/pdbsum/6ofp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofp ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BICD2_HUMAN BICD2_HUMAN] BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/BICD2_HUMAN BICD2_HUMAN] Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates and stabilizes the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (By similarity). Facilitates the binding of RAB6A to the Golgi by stabilizing its GTP-bound form. Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport via its interaction with RAB6A and recruitment of the dynein-dynactin motor complex (PubMed:25962623). Contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1. During G2 phase of the cell cycle, associates with RANBP2 at the nuclear pores and recruits dynein and dynactin to the nuclear envelope to ensure proper positioning of the nucleus relative to centrosomes prior to the onset of mitosis (By similarity).[UniProtKB:Q921C5]<ref>PMID:25962623</ref> 
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== Publication Abstract from PubMed ==
Dynein adaptors such as Bicaudal D2 (BicD2) recognize cargo for dynein-dependent transport, and cargo-bound adaptors are required to activate dynein for processive transport, but the mechanism of action is unknown. Here we report the X-ray structure of the cargo-binding domain of human BicD2 and investigate the structural dynamics of the coiled-coil. Our molecular dynamics simulations support the fact that BicD2 can switch from a homotypic coiled-coil registry, in which both helices of the homodimer are aligned, to an asymmetric registry, where a portion of one helix is vertically shifted, as both states are similarly stable and defined by distinct conformations of F743. The F743I variant increases dynein recruitment in the Drosophila homologue, whereas the human R747C variant causes spinal muscular atrophy. We report spontaneous registry shifts for both variants, which may be the cause for BicD2 hyperactivation and disease. We propose that a registry shift upon cargo binding may activate autoinhibited BicD2 for dynein recruitment.

Role of Coiled-Coil Registry Shifts in the Activation of Human Bicaudal D2 for Dynein Recruitment upon Cargo Binding.,Noell CR, Loh JY, Debler EW, Loftus KM, Cui H, Russ BB, Zhang K, Goyal P, Solmaz SR J Phys Chem Lett. 2019 Jul 22:4362-4367. doi: 10.1021/acs.jpclett.9b01865. PMID:31306018<ref>PMID:31306018</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ofp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cui H]]
[[Category: Debler EW]]
[[Category: Noell CR]]
[[Category: Solmaz SR]]