View source for 4nf9


==Structure of the Knl1/Nsl1 complex==
<StructureSection load='4nf9' size='340' side='right'caption='[[4nf9]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nf9]] is a 4 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=4NF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NF9 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=4nf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nf9 OCA], [https://pdbe.org/4nf9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nf9 RCSB], [https://www.ebi.ac.uk/pdbsum/4nf9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nf9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KNL1_HUMAN KNL1_HUMAN] Autosomal recessive primary microcephaly. A chromosomal aberration involving KNL1 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A. May give rise to a KMT2A-KNL1 fusion protein.<ref>PMID:12618766</ref>   The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/KNL1_HUMAN KNL1_HUMAN] Performs two crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Required for attachment of the kinetochores to the spindle microtubules. Directly links BUB1 and BUB1B to kinetochores. Part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore.<ref>PMID:15502821</ref> <ref>PMID:17981135</ref> <ref>PMID:18045986</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Faithful chromosome segregation is mandatory for cell and organismal viability. Kinetochores, large protein assemblies embedded in centromeric chromatin, establish a mechanical link between chromosomes and spindle microtubules. The KMN network, a conserved 10-subunit kinetochore complex, harbors the microtubule-binding interface. RWD domains in the KMN subunits Spc24 and Spc25 mediate kinetochore targeting of the microtubule-binding subunits by interacting with the Mis12 complex, a KMN subcomplex that tethers directly onto the underlying chromatin layer. Here, we show that Knl1, a KMN subunit involved in mitotic checkpoint signaling, also contains RWD domains that bind the Mis12 complex and that mediate kinetochore targeting of Knl1. By reporting the first 3D electron microscopy structure of the KMN network, we provide a comprehensive framework to interpret how interactions of RWD-containing proteins with the Mis12 complex shape KMN network topology. Our observations unveil a regular pattern in the construction of the outer kinetochore.

Modular Assembly of RWD Domains on the Mis12 Complex Underlies Outer Kinetochore Organization.,Petrovic A, Mosalaganti S, Keller J, Mattiuzzo M, Overlack K, Krenn V, De Antoni A, Wohlgemuth S, Cecatiello V, Pasqualato S, Raunser S, Musacchio A Mol Cell. 2014 Feb 20;53(4):591-605. doi: 10.1016/j.molcel.2014.01.019. Epub 2014, Feb 13. PMID:24530301<ref>PMID:24530301</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4nf9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Keller J]]
[[Category: Mattiuzzo M]]
[[Category: Mosalaganti S]]
[[Category: Musacchio A]]
[[Category: Overlack K]]
[[Category: Pasqualato S]]
[[Category: Petrovic A]]
[[Category: Raunser S]]
[[Category: Wohlgemuth S]]