| Structural highlights
4dzo is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | NonStd Res: | |
| Gene: | MAD1, MAD1L1, TXBP181 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[MD1L1_HUMAN] Defects in MAD1L1 are involved in the development and/or progression of various types of cancer.
Function
[MD1L1_HUMAN] Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. May recruit MAD2L1 to unattached kinetochores. Has a role in the correct positioning of the septum. Required for anchoring MAD2L1 to the nuclear periphery. Binds to the TERT promoter and represses telomerase expression, possibly by interfering with MYC binding.[1] [2] [3]
Publication Abstract from PubMed
The spindle checkpoint prevents aneuploidy by delaying anaphase onset until all sister chromatids achieve proper microtubule attachment. The kinetochore-bound checkpoint protein complex Mad1-Mad2 promotes the conformational activation of Mad2 and serves as a catalytic engine of checkpoint signaling. How Mad1 is targeted to kinetochores is not understood. Here, we report the crystal structure of the conserved C-terminal domain (CTD) of human Mad1. Mad1 CTD forms a homodimer and, unexpectedly, has a fold similar to those of the kinetochore-binding domains of Spc25 and Csm1. Nonoverlapping Mad1 fragments retain detectable kinetochore targeting. Deletion of the CTD diminishes, does not abolish, Mad1 kinetochore localization. Mutagenesis studies further map the functional interface of Mad1 CTD in kinetochore targeting and implicate Bub1 as its receptor. Our results indicate that CTD is a part of an extensive kinetochore-binding interface of Mad1, and rationalize graded kinetochore targeting of Mad1 during checkpoint signaling.
Structure of human Mad1 C-terminal domain reveals its involvement in kinetochore targeting.,Kim S, Sun H, Tomchick DR, Yu H, Luo X Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6549-54. Epub 2012 Apr 9. PMID:22493223[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jin DY, Kozak CA, Pangilinan F, Spencer F, Green ED, Jeang KT. Mitotic checkpoint locus MAD1L1 maps to human chromosome 7p22 and mouse chromosome 5. Genomics. 1999 Feb 1;55(3):363-4. PMID:10049595 doi:http://dx.doi.org/10.1006/geno.1998.5654
- ↑ Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell. 2003 Jun 27;113(7):881-9. PMID:12837246
- ↑ Nakano H, Funasaka T, Hashizume C, Wong RW. Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis. J Biol Chem. 2010 Apr 2;285(14):10841-9. doi: 10.1074/jbc.M110.105890. Epub 2010 , Feb 4. PMID:20133940 doi:http://dx.doi.org/10.1074/jbc.M110.105890
- ↑ Kim S, Sun H, Tomchick DR, Yu H, Luo X. Structure of human Mad1 C-terminal domain reveals its involvement in kinetochore targeting. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6549-54. Epub 2012 Apr 9. PMID:22493223 doi:10.1073/pnas.1118210109
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