Journal of Bioinformatics and Sequence Analysis
Subscribe to JBSA
Full Name*
Email Address*

Article Number - E93F45E5736


Vol.5(1), pp. 10-15 , January 2013
DOI: 10.5897/JBSA11.022
ISSN: 2141-2464



Full Length Research Paper

Generation of a 3D model for human cereblon using comparative modelling


Samina Bilal*, Shumaila Barkat Ali, Sahar Fazal and Asif Mir




Department of Computer Sciences and Bioinformatics, Mohammad Ali Jinnah University Islamabad Sihala Road, Pakistan.


Email: shumaila.ali86@gmail.com






 Accepted: 17 February 2012  Published: 28 January 2013

Copyright © 2013 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0


 

Three-dimensional (3D) protein structures provide helpful insights into the molecularassociation of a gene, its purpose also allow efficient drug designing experiments, such as the structure-based design of specific inhibitors. Recently, it has been shown that protein (cereblon) is involved in various tissues and brain and is revealed to be related with mental retardation. After this first report of cereblon (CRBN) involvement, it was necessary to further study this protein. Therefore a 3D structure of cereblon was developed using comparative modeling approach. By comparing the templates-target sequence, a model was created using MODELLER, a program for homology modeling. The accuracy of the predicted structure was checked using Ramachandran plot which showed that the residue falling in the favoured region was 88.4%. Thepredicted cereblon model can be used to understand the pathogenesis of mutations in cereblon that causes adenosine-5'-triphosphate (ATP)-dependent degradation of proteins in memory and learning.

 

Key words: CRBN, 3D structure, 1M4Y, MODELLER, comparative homology modeling.

 

Albrecht U, Sutcliffe JS, Cattanach BM (1997). Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat. Genet. 17:75-78 biologie/urbm/bioinfo/esypred/)
 
Costa RM, Federov NB, Kogan JH (2002). Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415:526-530
http://dx.doi.org/10.1038/nature711
PMid:11793011
 
Curry CJ, Stevenson RE, Aughton D (1997). Evaluation of mental retardation: recommendations of a Consensus Conference: American College of Medical Genetics. Am. J. Med. Genet. 72:468-477.
http://dx.doi.org/10.1002/(SICI)1096-8628(19971112)72:4<468::AID-AJMG18>3.0.CO;2-P
 
Darnell JC, Jensen KB, Jin P (2001). Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107:489-499
http://dx.doi.org/10.1016/S0092-8674(01)00566-9
 
Galdzicki Z, Siarey R, Pearce R (2001). On the cause of mental retardation in Down syndrome: extrapolation from full and segmental trisomy 16 mouse models. Brain Res. Rev. 35:115-145.
http://dx.doi.org/10.1016/S0926-6410(00)00074-4
 
Higgins JJ, Pucilowska J, Lombardi RQ, Rooney JP (2004). A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation. Neurology 63:1927-1931.
http://dx.doi.org/10.1212/01.WNL.0000146196.01316.A2
PMid:15557513 PMCid:PMC1201536
 
Higgins JJ, J Hao, BE Kososky (2008). Dysregulation of large conductance Ca2+ -activated K+ channel expression in nonsyndromal mental retardation due to a cerebelon p.R419X mutation. Neurogenetics. 9:219-223.
http://dx.doi.org/10.1007/s10048-008-0128-2
PMid:18414909
 
Higgins JJ, Rosen DR, Loveless JM, Clyman JC, Grau MJ (2000). A gene for nonsyndromic mental retardation maps to chromosome 3p25-pter. Neurology 55:335-340.
http://dx.doi.org/10.1212/WNL.55.3.335
PMid:10932263
 
Hooft RWW, Vriend G, Sander C, Abola EE (1993). Errors in protein structures. Nature 381: 272-272. (Server: http://swift.cmbi.kun.nl/WIWWWI/)
http://dx.doi.org/10.1038/381272a0
PMid:8692262
 
Jo S, Lee KH, Song S, Jung YK, Park CS (2005). Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain. J. Neurochem. 94:1212–1224
http://dx.doi.org/10.1111/j.1471-4159.2005.03344.x
PMid:16045448
 
Lambert C, Leonard N, De Bolle X, Depiereux E (2002). ESyPred3D: Prediction of proteins 3D structures. Bioinformatics 18(9):1250-1256. (Server:http://www.fundp.ac.be/sciences)
http://dx.doi.org/10.1093/bioinformatics/18.9.1250
 
Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993). PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst., 26: 283-291. (Server: http://www.csb.yale.edu/userguides/datamanip/procheck/)
http://dx.doi.org/10.1107/S0021889892009944
 
Lu B, Liu T, Crosby JA (2003). The ATP-dependent Lon protease of Mus musculus is a DNA-binding protein that is functionally conserved between yeast and mammals. Gene 306:45-55.
http://dx.doi.org/10.1016/S0378-1119(03)00403-7
 
Lund O, Nielsen M, Lundegaard C, Worning P (2002). X3M a Computer Program to Extract 3D Models. CASP5 conference A102. (Server:http://www.cbs.dtu.dk/services/CPHmodels/output.php)
 
Marti-Renom MA, Stuart AC, Fiser A, Sanchez R, Melo F, Sali A (2000). Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct. 29:291-325.
http://dx.doi.org/10.1146/annurev.biophys.29.1.291
PMid:10940251
 
Matsuura T, Sutcliffe JS, Fang P (1997). De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat. Genet. 15:74-77.
http://dx.doi.org/10.1038/ng0197-74
PMid:8988172
 
Morris AL, MacArthur MW, Hutchinson EG, Thornton JM (1992). Stereochemical quality of protein structure coordinates. Proteins 12:345-364.
http://dx.doi.org/10.1002/prot.340120407
PMid:1579569
 
Petrij F, Giles RH, Dauwerse HG (1995). Rubinstein–Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376:348–351
http://dx.doi.org/10.1038/376348a0
PMid:7630403
 
Roberto S, Andrej S (2000). Comparative protein structure modeling: Introduction and practical examples with MODELLER. In: Protein Structure Prediction: Methods and Protocols. Ed: Webster, D. M., 97-129. Humana Press.
 
Sali A (1998). 100,000 protein structures for the biologist. Nat. Struct. Biol. 5:1029-1032.
http://dx.doi.org/10.1038/4136
PMid:9846869
 
Sali A, Blundell TL (1993). Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234:779-815.
http://dx.doi.org/10.1006/jmbi.1993.1626
PMid:8254673
 
Shahbazian M, Young J, Yuva-Paylor L (2002). Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35:243-254.
http://dx.doi.org/10.1016/S0896-6273(02)00768-7
 
Vitkup D, Melamud E, Moult J, Sander C (2001). Completeness in structural genomics. Nat. Struct. Biol. 8(6):559-566.
http://dx.doi.org/10.1038/88640
PMid:11373627
 
Wang N, Gottesman S, Willingham MC (1993). A human mitochondrial ATPdependent protease that is highly homologous to bacterial Lon protease. Proc. Natl. Acad. Sci. USA 90:11247-11251.
http://dx.doi.org/10.1073/pnas.90.23.11247
PMid:8248235 PMCid:PMC47959
 
Wang YH, Amirhaeri S, Kang S (1994). Preferential nucleosome assembly at DNA triplet repeats from the myotonic dystrophy gene. Science 265:669-671.
http://dx.doi.org/10.1126/science.8036515
PMid:8036515
 
Wright SW, Tarjan G, Eyer L (1959). Investigation of families with two or more mentally defective siblings; clinical observations. Am. J. Dis. Child 97:445-463
http://dx.doi.org/10.1001/archpedi.1959.02070010447010
 
Xin W, Xiaohua N, Peilin C (2008). Primary function analysis of human mental retardation related gene CRBN. Mol. Biol. Rep. 35:251-256.
http://dx.doi.org/10.1007/s11033-007-9077-3
PMid:17380424
 
Xing J, Ginty DD, Greenberg ME (1996). Coupling of the RASMAPK pathway to gene activation by RSK2, a growth factor regulated CREB kinase. Science 273:959-963
http://dx.doi.org/10.1126/science.273.5277.959
PMid:8688081
 
Yang EJ, Yoon JH, Min do S (2004). LIM kinase 1 activates cAMP-responsive element-binding protein during the neuronal differentiation of immortalized hippocampal progenitor cells. J. Biol. Chem. 279:8903–8910.
http://dx.doi.org/10.1074/jbc.M311913200
PMid:14684741

 


APA (2013). Generation of a 3D model for human cereblon using comparative modelling. Journal of Bioinformatics and Sequence Analysis, 5(1), 10-15.
Chicago Samina Bilal, Shumaila Barkat Ali, Sahar Fazal and Asif Mir. "Generation of a 3D model for human cereblon using comparative modelling." Journal of Bioinformatics and Sequence Analysis 5, no. 1 (2013): 10-15.
MLA Samina Bilal, et al. "Generation of a 3D model for human cereblon using comparative modelling." Journal of Bioinformatics and Sequence Analysis 5.1 (2013): 10-15.
   
DOI 10.5897/JBSA11.022
URL http://academicjournals.org/journal/JBSA/article-abstract/E93F45E5736

Subscription Form