| Structural highlights
Function
[NDEL1_HUMAN] Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ndel1 and Nde1 are homologous and evolutionarily conserved proteins, with critical roles in cell division, neuronal migration, and other physiological phenomena. These functions are dependent on their interactions with the retrograde microtubule motor dynein and with its regulator Lis1--a product of the causal gene for isolated lissencephaly sequence (ILS) and Miller-Dieker lissencephaly. The molecular basis of the interactions of Ndel1 and Nde1 with Lis1 is not known. Here, we present a crystallographic study of two fragments of the coiled-coil domain of Ndel1, one of which reveals contiguous high-quality electron density for residues 10-166, the longest such structure reported by X-ray diffraction at high resolution. Together with complementary solution studies, our structures reveal how the Ndel1 coiled coil forms a stable parallel homodimer and suggest mechanisms by which the Lis1-interacting domain can be regulated to maintain a conformation in which two supercoiled alpha helices cooperatively bind to a Lis1 homodimer.
The structure of the coiled-coil domain of Ndel1 and the basis of its interaction with Lis1, the causal protein of Miller-Dieker lissencephaly.,Derewenda U, Tarricone C, Choi WC, Cooper DR, Lukasik S, Perrina F, Tripathy A, Kim MH, Cafiso DS, Musacchio A, Derewenda ZS Structure. 2007 Nov;15(11):1467-81. PMID:17997972[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yan X, Li F, Liang Y, Shen Y, Zhao X, Huang Q, Zhu X. Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle. Mol Cell Biol. 2003 Feb;23(4):1239-50. PMID:12556484
- ↑ Hayashi MA, Portaro FC, Bastos MF, Guerreiro JR, Oliveira V, Gorrao SS, Tambourgi DV, Sant'Anna OA, Whiting PJ, Camargo LM, Konno K, Brandon NJ, Camargo AC. Inhibition of NUDEL (nuclear distribution element-like)-oligopeptidase activity by disrupted-in-schizophrenia 1. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3828-33. Epub 2005 Feb 23. PMID:15728732 doi:http://dx.doi.org/10.1073/pnas.0500330102
- ↑ Liang Y, Yu W, Li Y, Yang Z, Yan X, Huang Q, Zhu X. Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein. J Cell Biol. 2004 Feb 16;164(4):557-66. PMID:14970193 doi:http://dx.doi.org/10.1083/jcb.200308058
- ↑ Guo J, Yang Z, Song W, Chen Q, Wang F, Zhang Q, Zhu X. Nudel contributes to microtubule anchoring at the mother centriole and is involved in both dynein-dependent and -independent centrosomal protein assembly. Mol Biol Cell. 2006 Feb;17(2):680-9. Epub 2005 Nov 16. PMID:16291865 doi:http://dx.doi.org/10.1091/mbc.E05-04-0360
- ↑ Vergnolle MA, Taylor SS. Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes. Curr Biol. 2007 Jul 3;17(13):1173-9. PMID:17600710 doi:http://dx.doi.org/10.1016/j.cub.2007.05.077
- ↑ Derewenda U, Tarricone C, Choi WC, Cooper DR, Lukasik S, Perrina F, Tripathy A, Kim MH, Cafiso DS, Musacchio A, Derewenda ZS. The structure of the coiled-coil domain of Ndel1 and the basis of its interaction with Lis1, the causal protein of Miller-Dieker lissencephaly. Structure. 2007 Nov;15(11):1467-81. PMID:17997972 doi:http://dx.doi.org/10.1016/j.str.2007.09.015
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