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Solution NMR structures of immunoglobulin-like domains 7 and 12 from obscurin-like protein 1 contribute to the structural coverage of the human cancer protein interaction network

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Journal of Structural and Functional Genomics

Abstract

High-quality solution NMR structures of immunoglobulin-like domains 7 and 12 from human obscurin-like protein 1 were solved. The two domains share 30 % sequence identity and their structures are, as expected, rather similar. The new structures contribute to structural coverage of human cancer associated proteins. Mutations of Arg 812 in domain 7 cause the rare 3-M syndrome, and this site is located in a surface area predicted to be involved in protein–protein interactions.

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Abbreviations

CUL7:

Cullin7

CCDC8:

Coiled-coil domain containing protein 8

DSS:

4,4-Dimethyl-4-silapentane-1-sulfonate sodium salt

DTT:

Dithiothreitol

FBXW8:

Fbox and WD repeat containing protein 8

HCPIN:

Human Cancer Pathway Interaction Network

Ig-like:

Immunoglobulin-like

MES:

2-(N-morpholino)ethanesulfonic acid

MAPK:

Mitogen-activated protein kinase

NESG:

Northeast Structural Genomics Consortium

NOESY:

Nuclear Overhauser enhancement spectroscopy

OBSL1:

Obscurin-like protein 1

PDB:

Protein Data Bank

RDC:

Residual dipolar coupling

RMSD:

Root mean square deviation

TLR:

Toll-like receptor

Tris:

Tris(hydroxymethyl)aminomethane

References

  1. Geisler SB, Robinson D, Hauringa M, Raeker MO, Borisov AB, Westfall MV, Russell MW (2007) Obscurin-like 1, OBSL1, is a novel cytoskeletal protein related to obscurin. Genomics 89:521–531

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Fukuzawa A, Lange S, Holt M, Vihola A, Carmignac V, Ferreiro A, Udd B, Gautel M (2008) Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band—implications for hereditary myopathies. J Cell Sci 121:1841–1851

  3. Litterman N, Ikeuchi Y, Gallardo G, O’Connell BC, Sowa ME, Gygi SP, Harper JW, Bonni A (2011) An OBSL1-Cul7 Fbxw8 ubiquitin ligase signaling mechanism regulates golgi morphology and dendrite patterning. PLoS Biol 9:e1001060

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Huber C, Fradin M, Edouard T, Le Merrer M, Alanay Y, Da Silva DB, David A, Hamamy H, van Hest L, Lund AM, Michaud J, Oley C, Patel C, Rajab A, Skidmore DL, Stewart H, Tauber M, Munnich A, Cormier-Daire V (2010) OBSL1 mutations in 3-M syndrome are associated with a modulation of IGFBP2 and IGFBP5 expression levels. Hum Mutat 31:20–26

    Article  CAS  PubMed  Google Scholar 

  5. Hanson D, Murray PG, Sud A, Temtamy SA, Aglan M, Superti-Furga A, Holder SE, Urquhart J, Hilton E, Manson FDC, Scambler P, Black GCM, Clayton PE (2009) The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1. Am J Hum Genet 84:801–806

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Sasaki K, Okamoto N, Kosaki K, Yorifuji T, Shimokawa O, Mishima H, Yoshiura K, Harada N (2011) Maternal uniparental isodisomy and heterodisomy on chromosome 6 encompassing a CUL7 gene mutation causing 3 M syndrome. Clin Genet 80:478–483

    Article  CAS  PubMed  Google Scholar 

  7. Hanson D, Murray PG, O’Sullivan J, Urquhart J, Daly S, Bhaskar SS, Biesecker LG, Skae M, Smith C, Cole T, Kirk J, Chandler K, Kingston H, Donnai D, Clayton PE, Black GC (2011) Exome sequencing identifies CCDC8 mutations in 3-M syndrome, suggesting that CCDC8 contributes in a pathway with CUL7 and OBSL1 to control human growth. Am J Hum Genet 89:148–153

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Clayton PE, Hanson D, Magee L, Murray PG, Saunders E, Abu-Amero SN, Moore GE, Black GCM (2012) Exploring the spectrum of 3-M syndrome, a primordial short stature disorder of disrupted ubiquitination. Clin Endocrinol 77:335–342

    Article  CAS  Google Scholar 

  9. Hanson D, Murray PG, Black GCM, Clayton PE (2011) The genetics of 3-M syndrome: unravelling a potential new regulatory growth pathway. Horm Res Paediatr 76:369–378

    Article  CAS  PubMed  Google Scholar 

  10. Varjosalo M, Keskitalo S, Van Drogen A, Nurkkala H, Vichalkovski A, Aebersold R, Gstaiger M (2013) The protein interaction landscape of the human CMGC kinase group. Cell Rep 3:1306–1320

    Article  CAS  PubMed  Google Scholar 

  11. Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer ELL, Eddy SR, Bateman A (2010) The Pfam protein families database. Nucleic Acids Res 38:D211–D222

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Sauer F, Vahokoski J, Song Y-H, Wilmanns M (2010) Molecular basis of the head-to-tail assembly of giant muscle proteins obscurin-like 1 and titin. EMBO Rep 11:534–540

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Pernigo S, Fukuzawa A, Bertz M, Holt M, Rief M, Steiner RA, Gautel M (2010) Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex. Proc Natl Acad Sci USA 107:2908–2913

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Bork P, Holm L, Sander C (1994) The immunoglobulin fold: structural classification, sequence patterns and common core. J Mol Biol 242:309–320

    CAS  PubMed  Google Scholar 

  16. Huang YJ, Hang D, Lu LJ, Tong L, Gerstein MB, Montelione GT (2008) Targeting the human cancer pathway protein interaction network by structural genomics. Mol Cell Proteomics 7:2048–2060

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Xiao R, Anderson S, Aramini J, Belote R, Buchwald WA, Ciccosanti C, Conover K, Everett JK, Hamilton K, Huang YJ, Janjua H, Jiang M, Kornhaber GJ, Lee DY, Locke JY, Ma L-C, Maglaqui M, Mao L, Mitra S, Patel D, Rossi P, Sahdev S, Sharma S, Shastry R, Swapna GVT, Tong SN, Wang D, Wang H, Zhao L, Montelione GT, Acton TB (2010) The high-throughput protein sample production platform of the Northeast Structural Genomics Consortium. J Struct Biol 172:21–33

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Acton TB, Xiao R, Anderson S, Aramini J, Buchwald WA, Ciccosanti C, Conover K, Everett J, Hamilton K, Huang YJ, Janjua H, Kornhaber G, Lau J, Lee DY, Liu GH, Maglaqui M, Ma LC, Mao L, Patel D, Rossi P, Sahdev S, Shastry R, Swapna GVT, Tang YF, Tong SC, Wang DY, Wang H, Zhao L, Montelione GT (2011) Preparation of protein samples for NMR structure, function, and small-molecule screening studies. Methods Enzymol 493:21–60

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Acton TB, Gunsalus KC, Xiao R, Ma LC, Aramini J, Baran MC, Chiang Y-W, Climent T, Cooper B, Denissova NG, Douglas SM, Everett JK, Ho CK, Macapagal D, Rajan PK, Shastry R, Shih LY, Swapna GVT, Wilson M, Wu M, Gerstein M, Inouye M, Hunt JF, Montelione GT (2005) Robotic cloning and protein production platform of the Northeast Structural Genomics Consortium. Methods Enzymol 394:210–243

    Article  CAS  PubMed  Google Scholar 

  20. Neri D, Szyperski T, Otting G, Senn H, Wuthrich K (1989) Stereospecific nuclear magnetic resonance assignments of the methyl groups of valine and leucine in the DNA-binding domain of the 434 repressor by biosynthetically directed fractional 13C labeling. Biochemistry 28:7510–7516

    Article  CAS  PubMed  Google Scholar 

  21. Moseley HNB, Monleon D, Montelione GT (2001) Automatic determination of protein backbone resonance assignments from triple resonance nuclear magnetic resonance data. Methods Enzymol 339:91–108

    Article  CAS  PubMed  Google Scholar 

  22. Zimmerman DE, Kulikowski CA, Huang YP, Feng WQ, Tashiro M, Shimotakahara S, Chien CY, Powers R, Montelione GT (1997) Automated analysis of protein NMR assignments using methods from artificial intelligence. J Mol Biol 269:592–610

    Article  CAS  PubMed  Google Scholar 

  23. Moseley HNB, Sahota G, Montelione GT (2004) Assignment validation software suite for the evaluation and presentation of protein resonance assignment data. J Biomol NMR 28:341–355

    Article  CAS  PubMed  Google Scholar 

  24. Huang YJ, Powers R, Montelione GT (2005) Protein NMR recall, precision, and F-measure scores (RPF scores): structure quality assessment measures based on information retrieval statistics. J Am Chem Soc 127:1665–1674

    Article  CAS  PubMed  Google Scholar 

  25. Liu G, Shen Y, Atreya HS, Parish D, Shao Y, Sukumaran DK, Xiao R, Yee A, Lemak A, Bhattacharya A, Acton TA, Arrowsmith CH, Montelione GT, Szyperski T (2005) NMR data collection and analysis protocol for high-throughput protein structure determination. Proc Natl Acad Sci USA 102:10487–10492

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Guntert P, Mumenthaler C, Wuthrich K (1997) Torsion angle dynamics for NMR structure calculation with the new program DYANA. J Mol Biol 273:283–298

    Article  CAS  PubMed  Google Scholar 

  27. Herrmann T, Güntert P, Wüthrich K (2002) Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA. J Mol Biol 319:209–227

    Article  CAS  PubMed  Google Scholar 

  28. Huang YJ, Tejero R, Powers R, Montelione GT (2006) A topology-constrained distance network algorithm for protein structure determination from NOESY data. Proteins 62:587–603

    Article  CAS  PubMed  Google Scholar 

  29. Cornilescu G, Delaglio F, Bax A (1999) Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR 13:289–302

    Article  CAS  PubMed  Google Scholar 

  30. Liu Y, Prestegard JH (2009) Measurement of one and two bond N–C couplings in large proteins by TROSY-based J-modulation experiments. J Magn Reson 200:109–118

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL (1998) Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr Sect D Biol Crystallogr 54:905–921

    Article  CAS  Google Scholar 

  32. Bhattacharya A, Tejero R, Montelione GT (2007) Evaluating protein structures determined by structural genomics consortia. Proteins 66:778–795

    Article  CAS  PubMed  Google Scholar 

  33. Holm L, Sander C (1995) Dali: a network tool for protein structure comparison. Trends Biochem Sci 20:478–480

    Article  CAS  PubMed  Google Scholar 

  34. Zhang QC, Deng L, Fisher M, Guan J, Honig B, Petrey D (2011) PredUs: a web server for predicting protein interfaces using structural neighbors. Nucleic Acids Res 39:W283–W287

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Zhang QC, Petrey D, Norel R, Honig BH (2010) Protein interface conservation across structure space. Proc Natl Acad Sci USA 107:10896–10901

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Institutes of Health, grant number: U54 GM094597 (T.S., J.H.P. and G.T.M.).

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Authors and Affiliations

  1. Department of Chemistry, The State University of New York at Buffalo and Northeast Structural Genomics Consortium, Buffalo, NY, 14260, USA

    Surya V. S. R. K. Pulavarti & Thomas Szyperski

  2. Complex Carbohydrate Research Center and Northeast Structural Genomics Consortium, University of Georgia, Athens, GA, 30602, USA

    Kari Pederson & James H. Prestegard

  3. Center of Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey and Northeast Structural Genomics Consortium, Piscataway, NJ, 08854, USA

    Yuanpeng J. Huang, Thomas B. Acton, Rong Xiao, John K. Everett & Gaetano T. Montelione

  4. Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, UMDNJ, Piscataway, NJ, 08854, USA

    Gaetano T. Montelione

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  1. Surya V. S. R. K. Pulavarti
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  2. Yuanpeng J. Huang
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Correspondence to Thomas Szyperski.

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Pulavarti, S.V.S.R.K., Huang, Y.J., Pederson, K. et al. Solution NMR structures of immunoglobulin-like domains 7 and 12 from obscurin-like protein 1 contribute to the structural coverage of the human cancer protein interaction network. J Struct Funct Genomics 15, 209–214 (2014). https://doi.org/10.1007/s10969-014-9185-y

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  • DOI: https://doi.org/10.1007/s10969-014-9185-y

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