Structural Features and Chaperone Activity of the NudC Protein Family

Overview

Journal J Mol Biol

Publisher Elsevier

Specialties Microbiology
Molecular Biology

Date 2011 May 3

PMID 21530541

Citations 19

Authors

Meiying Zheng

Tomasz Cierpicki

Alexander J Burdette

Darkhan Utepbergenov

Pawel L Janczyk

Urszula Derewenda

P Todd Stukenberg

Kim A Caldwell

Zygmunt S Derewenda

Affiliations

Soon will be listed here.

Abstract

The NudC family consists of four conserved proteins with representatives in all eukaryotes. The archetypal nudC gene from Aspergillus nidulans is a member of the nud gene family that is involved in the maintenance of nuclear migration. This family also includes nudF, whose human orthologue, Lis1, codes for a protein essential for brain cortex development. Three paralogues of NudC are known in vertebrates: NudC, NudC-like (NudCL), and NudC-like 2 (NudCL2). The fourth distantly related member of the family, CML66, contains a NudC-like domain. The three principal NudC proteins have no catalytic activity but appear to play as yet poorly defined roles in proliferating and dividing cells. We present crystallographic and NMR studies of the human NudC protein and discuss the results in the context of structures recently deposited by structural genomics centers (i.e., NudCL and mouse NudCL2). All proteins share the same core CS domain characteristic of proteins acting either as cochaperones of Hsp90 or as independent small heat shock proteins. However, while NudC and NudCL dimerize via an N-terminally located coiled coil, the smaller NudCL2 lacks this motif and instead dimerizes as a result of unique domain swapping. We show that NudC and NudCL, but not NudCL2, inhibit the aggregation of several target proteins, consistent with an Hsp90-independent heat shock protein function. Importantly, and in contrast to several previous reports, none of the three proteins is able to form binary complexes with Lis1. The availability of structural information will be of help in further studies on the cellular functions of the NudC family.

Citing Articles

NUDC Is Critical for Mitosis and Postmitotic Cell Maintenance Through Its Modulation of Dynein and Actin Cytoskeletal Reorganization.

Garner M, Gross A Adv Exp Med Biol. 2025; 1468:453-457.

PMID: 39930237 DOI: 10.1007/978-3-031-76550-6_74.

Small Sized Yet Powerful: Nuclear Distribution C Proteins in Plants.

Vassileva V, Georgieva M, Todorov D, Mishev K Plants (Basel). 2024; 13(1).

PMID: 38202427 PMC: 10780334. DOI: 10.3390/plants13010119.

NudC regulated Lis1 stability is essential for the maintenance of dynamic microtubule ends in axon terminals.

Kawano D, Pinter K, Chlebowski M, Petralia R, Wang Y, Nechiporuk A iScience. 2022; 25(10):105072.

PMID: 36147950 PMC: 9485903. DOI: 10.1016/j.isci.2022.105072.

NudCL2 is an autophagy receptor that mediates selective autophagic degradation of CP110 at mother centrioles to promote ciliogenesis.

Liu M, Zhang W, Li M, Feng J, Kuang W, Chen X Cell Res. 2021; 31(11):1199-1211.

PMID: 34480124 PMC: 8563757. DOI: 10.1038/s41422-021-00560-3.

NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration.

Liu M, Xu Z, Zhang C, Yang C, Feng J, Lu Y Front Cell Dev Biol. 2021; 9:671233.

PMID: 34262899 PMC: 8273881. DOI: 10.3389/fcell.2021.671233.

References

Feng Y, Olson E, Stukenberg P, Flanagan L, Kirschner M, Walsh C . LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome. Neuron. 2001; 28(3):665-79. DOI: 10.1016/s0896-6273(00)00145-8. View

Aumais J, Williams S, Luo W, Nishino M, Caldwell K, Caldwell G . Role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis. J Cell Sci. 2003; 116(Pt 10):1991-2003. DOI: 10.1242/jcs.00412. View

Guo L, Groenendyk J, Papp S, Dabrowska M, Knoblach B, Kay C . Identification of an N-domain histidine essential for chaperone function in calreticulin. J Biol Chem. 2003; 278(50):50645-53. DOI: 10.1074/jbc.M309497200. View

Hartmann T, Mattern E, Wiedemann N, van Doorn R, Willemze R, Niikura T . Identification of selectively expressed genes and antigens in CTCL. Exp Dermatol. 2007; 17(4):324-34. DOI: 10.1111/j.1600-0625.2007.00637.x. View

Perez D, Hoyer J, Johnson A, Moody Z, Lopez J, Kaplinsky N . BOBBER1 is a noncanonical Arabidopsis small heat shock protein required for both development and thermotolerance. Plant Physiol. 2009; 151(1):241-52. PMC: 2735987. DOI: 10.1104/pp.109.142125. View

Weaver A, SULLIVAN W, Felts S, Owen B, Toft D . Crystal structure and activity of human p23, a heat shock protein 90 co-chaperone. J Biol Chem. 2000; 275(30):23045-52. DOI: 10.1074/jbc.M003410200. View

Nishino M, Kurasawa Y, Evans R, Lin S, Brinkley B, Yu-Lee L . NudC is required for Plk1 targeting to the kinetochore and chromosome congression. Curr Biol. 2006; 16(14):1414-21. DOI: 10.1016/j.cub.2006.05.052. View

Lupas A, Van Dyke M, Stock J . Predicting coiled coils from protein sequences. Science. 1991; 252(5009):1162-4. DOI: 10.1126/science.252.5009.1162. View

Tarricone C, Perrina F, Monzani S, Massimiliano L, Kim M, Derewenda Z . Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. Neuron. 2004; 44(5):809-21. DOI: 10.1016/j.neuron.2004.11.019. View

10.

Dawe A, Caldwell K, Harris P, Morris N, Caldwell G . Evolutionarily conserved nuclear migration genes required for early embryonic development in Caenorhabditis elegans. Dev Genes Evol. 2001; 211(8-9):434-41. DOI: 10.1007/s004270100176. View

11.

Srivastava M, Begovic E, Chapman J, Putnam N, Hellsten U, Kawashima T . The Trichoplax genome and the nature of placozoans. Nature. 2008; 454(7207):955-60. DOI: 10.1038/nature07191. View

12.

Pan R, Yang Y, Wei M, Yu X, Ge Y, Xu P . A microtubule associated protein (hNUDC) binds to the extracellular domain of thrombopoietin receptor (Mpl). J Cell Biochem. 2005; 96(4):741-50. DOI: 10.1002/jcb.20573. View

13.

Morris R, Perrakis A, Lamzin V . ARP/wARP and automatic interpretation of protein electron density maps. Methods Enzymol. 2003; 374:229-44. DOI: 10.1016/S0076-6879(03)74011-7. View

14.

Nery F, Zeng J, Niland B, Hewett J, Farley J, Irimia D . TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton. J Cell Sci. 2008; 121(Pt 20):3476-86. PMC: 3539201. DOI: 10.1242/jcs.029454. View

15.

Wang Q, Li M, Wang Y, Zhang Y, Jin S, Xie G . RNA interference targeting CML66, a novel tumor antigen, inhibits proliferation, invasion and metastasis of HeLa cells. Cancer Lett. 2008; 269(1):127-38. DOI: 10.1016/j.canlet.2008.04.035. View

16.

Derewenda U, Tarricone C, Choi W, Cooper D, Lukasik S, Perrina F . 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; 15(11):1467-81. DOI: 10.1016/j.str.2007.09.015. View

17.

Kajan L, Rychlewski L . Evaluation of 3D-Jury on CASP7 models. BMC Bioinformatics. 2007; 8:304. PMC: 2040163. DOI: 10.1186/1471-2105-8-304. View

18.

Wei M, Yang Y, Ge Y, Xu P . Functional characterization of hNUDC as a novel accumulator that specifically acts on in vitro megakaryocytopoiesis and in vivo platelet production. J Cell Biochem. 2006; 98(2):429-39. DOI: 10.1002/jcb.20803. View

19.

Bateman A, Birney E, Cerruti L, Durbin R, Etwiller L, Eddy S . The Pfam protein families database. Nucleic Acids Res. 2001; 30(1):276-80. PMC: 99071. DOI: 10.1093/nar/30.1.276. View

20.

Miller B, Zhang M, Gocke C, de Souza C, Osmani A, Lynch C . A homolog of the fungal nuclear migration gene nudC is involved in normal and malignant human hematopoiesis. Exp Hematol. 1999; 27(4):742-50. DOI: 10.1016/s0301-472x(98)00074-5. View