Differential dynamics of RAS isoforms in GDP- and GTP-bound states

Proteins: Structure, Function and Bioinformatics

Volumn 83, Issue 6, 2015, Pages 1091-1106

  Kapoor, Abhijeet ^a   Travesset, Alex ^a  

^a IOWA STATE UNIVERSITY   (United States)

Author keywords

GEF; Mechanism; Molecular dynamics; RAS; Surface pockets

Indexed keywords

GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; ISOPROTEIN; K RAS PROTEIN; NUCLEOTIDE; RAS PROTEIN;

ARTICLE; CONFORMATION; CRYSTAL STRUCTURE; DYNAMICS; MEMBRANE; MOLECULAR DYNAMICS; ONCOGENE N RAS; PRIORITY JOURNAL; PROTEIN INTERACTION; SIMULATION; TEMPERATURE; WILD TYPE; CHEMISTRY; METABOLISM; STATIC ELECTRICITY; SURFACE PROPERTY;

GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; MOLECULAR DYNAMICS SIMULATION; PROTEIN ISOFORMS; RAS PROTEINS; STATIC ELECTRICITY; SURFACE PROPERTIES;

EID: 84929654326     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.24805     Document Type: Article

References (50)

1. Milburn M, Tong L, deVos A, Brunger A, Yamaizumi Z, Nishimura S, Kim S. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science 1990; 247:939-945.
2. White MA, Nicolette C, Minden A, Polverino A, Aelst LV, Karin M, Wigler MH. Multiple ras functions can contribute to mammalian cell transformation. Cell 1995; 80:533-541.
3. Wennerberg K, Rossman KL, Der CJ. The ras superfamily at a glance. J Cell Sci 2005; 118:843-846.
4. Rebollo A, Martinez-A C. Ras proteins: recent advances and new functions. Blood 1999; 94:2971-2980.
5. Bos JL, Rehmann H, Wittinghofer A. Gefs and gaps: critical elements in the control of small g proteins. Cell 2007; 129:865-877.
6. Downward J. Targeting ras signalling pathways in cancer therapy. Nat Rev Cancer 2003; 3:11-22.
7. Schubbert S, Shannon K, Bollag G. Hyperactive ras in developmental disorders and cancer. Nat Rev Cancer 2007; 7:295-308.
8. Scheffzek K, Ahmadian MR, Kabsch W, Wiesmüller L, Lautwein A, Schmitz F, Wittinghofer A. The ras-rasgap complex: structural basis for gtpase activation and its loss in oncogenic ras mutants. Science 1997; 277:333-339.
9. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J. The structural basis of the activation of Ras by Sos. Nature 1998; 394:337-343.
10. Ford B, Hornak V, Kleinman H, Nassar N. Structure of a transient intermediate for gtp hydrolysis by ras. Structure. 2006; 14:427-436.
11. Hall BE, Bar-Sagi D, Nassar N. The structural basis for the transition from ras-gtp to ras-gdp. Proc Natl Acad Sci USA 2002; 99:12138-12142.
12. Sung YJ, Carter M, Zhong JM, Hwang YW. Mutagenesis of the h-ras p21 at glycine-60 residue disrupts gtp-induced conformational change. Biochemistry 1995; 34:3470-3477.
13. Spoerner M, Herrmann C, Vetter IR, Kalbitzer HR, Wittinghofer A. Dynamic properties of the ras switch I region and its importance for binding to effectors. Proc Natl Acad Sci USA 2001; 98:4944-4949.
14. Hall BE, Yang SS, Boriack-Sjodin PA, Kuriyan J, Bar-Sagi D. Structure-based mutagenesis reveals distinct functions for ras switch 1 and switch 2 in sos-catalyzed guanine nucleotide exchange. J Biol Chem 2001; 276:27629-27637.
15. Ma J, Karplus M. Molecular switch in signal transduction: reaction paths of the conformational changes in ras p21. Proc Natl Acad Sci USA 1997; 94:11905-11910.
16. Gorfe AA, Grant BJ, McCammon JA. Mapping the nucleotide and isoform-dependent structural and dynamical features of ras proteins. Structure 2008; 16:885-896.
17. Grant BJ, Gorfe AA, McCammon JA. Ras conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics. PLoS Comput Biol 5:e1000325, 03, 2009.
18. Kobayashi C, Saito S. Relation between the conformational heterogeneity and reaction cycle of ras: molecular simulation of ras. Biophys J 2010; 99:3726-3734.
19. Raimondi F, Portella G, Orozco M, Fanelli F. Nucleotide binding switches the information flow in ras gtpases. PLoS Comput Biol 2011; 7:e1001098-03.
20. Spiegel J, Cromm PM, Zimmermann G, Grossmann TN, Waldmann H. Small-molecule modulation of ras signaling. Nat Chem Biol 2014; 10:613-622.
21. Castellano E, Santos E. Functional specificity of ras isoforms: so similar but so different. Genes Cancer 2011; 2:216-231.
22. Wolfman A. Ras isoform-specific signaling: location, location, location. Sci STKE 2001; 2001:pe2-pe2
23. Hancock, J. F. Ras proteins: different signals from different locations. Nat Rev Mol Cell Biol 2003;4:373-385.
24. Hancock JF, Parton RG. Ras plasma membrane signalling platforms. Biochem J 2005; 389:1-11.
25. Ehrhardt A, David MD, Ehrhardt GRA, Schrader JW. Distinct mechanisms determine the patterns of differential activation of h-ras, n-ras, k-ras 4b, and m-ras by receptors for growth factors or antigen. Mol Cell Biol 2004; 24:6311-6323.
26. Ehrhardt A, Ehrhardt GR, Guo X, Schrader JW. Ras and relatives-job sharing and networking keep an old family together. Exp Hematol 2002; 30:1089-1106.
27. Jones MK, Jackson JH. Ras-grf activates ha-ras, but not n-ras or k-ras 4b, protein in vivo. J Biol Chem 1998; 273:1782-1787.
28. Clyde-Smith J, Silins G, Gartside M, Grimmond S, Etheridge M, Apolloni A, Hayward N, Hancock JF. Characterization of rasgrp2, a plasma membrane-targeted, dual specificity ras/rap exchange factor. J Biol Chem 2000; 275:32260-32267.
29. Jaumot M, Yan J, Clyde-Smith J, Sluimer J, Hancock JF. The linker domain of the ha-ras hypervariable region regulates interactions with exchange factors, raf-1 and phosphoinositide 3-kinase. J Biol Chem 2002; 277:272-278.
30. Yan J, Roy S, Apolloni A, Lane A, Hancock JF. Ras isoforms vary in their ability to activate raf-1 and phosphoinositide 3-kinase. J Biol Chem 1998; 273:24052-24056.
31. Rodriguez-Viciana P, Warne PH, Khwaja A, Marte BM, Pappin D, Das P, Waterfield MD, Ridley A, Downward J. Role of phosphoinositide 3-oh kinase in cell transformation and control of the actin cytoskeleton by ras. Cell 1997; 89:457-467.
32. Lukman S, Grant BJ, Gorfe AA, Grant GH, McCammon JA. The distinct conformational dynamics of k-ras and h-ras a59g. PLoS Comput Biol 2010; 6
33. Kapoor A, Travesset A. Mechanism of the exchange reaction in hras from multiscale modeling. PLoS One 2014; 9:e108846-10.
34. Grant BJ, Lukman S, Hocker HJ, Sayyah J, Brown JH, McCammon JA, Gorfe AA. Novel allosteric sites on ras for lead generation. PLoS One 2011; 6:e25711
35. Maurer T, Garrenton LS, Oh A, Pitts K, Anderson DJ, Skelton NJ, Fauber BP, Pan B, Malek S, Stokoe D, Ludlam MJC, Bowman KK, Wu J, Giannetti AM, Starovasnik MA, Mellman I, Jackson PK, Rudolph J, Wang W, Fang G. Small-molecule ligands bind to a distinct pocket in ras and inhibit sos-mediated nucleotide exchange activity. Proc Natl Acad Sci USA 2012; 109:5299-5304.
36. Sun Q, Burke JP, Phan J, Burns MC, Olejniczak ET, Waterson AG, Lee T, Rossanese OW, Fesik SW. Discovery of small molecules that bind to k-ras and inhibit sos-mediated activation. Angew Chem Int Ed 2012; 51:6140-6143.
37. Ostrem J, Peters U, Sos M, Wells J, Shokat K. Kras(g12c) inhibitors allosterically control gtp affinity and effector interactions. Nature 2013; 503:548-551.
38. Shima F, Yoshikawa Y, Ye M, Araki M, Matsumoto S, Liao J, Hu L, Sugimoto T, Ijiri Y, Takeda A, Nishiyama Y, Sato C, Muraoka S, Tamura A, Osoda T, Tsuda Ki, Miyakawa T, Fukunishi H, Shimada J, Kumasaka T, Yamamoto M, Kataoka T. In silico discovery of small-molecule ras inhibitors that display antitumor activity by blocking the ras-effector interaction. Proc Natl Acad Sci 2013; 110:8182-8187.
39. Hocker HJ, Cho KJ, Chen CYK, Rambahal N, Sagineedu SR, Shaari K, Stanslas J, Hancock JF, Gorfe AA. Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic ras function. Proc Natl Acad Sci USA 2013; 110:10201-10206.
40. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kalé L, Schulten K. Scalable molecular dynamics with namd. J Comput Chem 2005; 26:1781-1802.
41. MacKerell, AD, Bashford D, Bellott Dunbrack, RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiórkiewicz-Kuczera J, Yin D, Karplus M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 1998; 102:3586-3616.
42. MacKerell AD, Feig M, Brooks CL. Improved treatment of the protein backbone in empirical force fields. J Am Chem Soc 2004; 126:698-699. PMID: 14733527.
43. Humphrey W, Dalke A, Schulten K. VMD-visual molecular dynamics. J Mol Graphics 1996; 14:33-38.
44. Schmidtke P, Bidon-Chanal A, Luque FJ, Barril X. Mdpocket: open-source cavity detection and characterization on molecular dynamics trajectories. Bioinformatics 2011; 27:3276-3285.
45. Vetter IR, Wittinghofer A. The guanine nucleotide-binding switch in three dimensions. Science 2001; 294:1299-1304.
46. Gorfe AA, Hanzal-Bayer M, Abankwa D, Hancock JF, McCammon JA. Structure and dynamics of the full-length lipid-modified h-ras protein in a 1, 2-dimyristoylglycero-3-phosphocholine bilayer. J Med Chem 2007; 50:674-684. PMID: 17263520.
47. Abankwa D, Hanzal-Bayer M, Ariotti N, Plowman SJ, Gorfe AA, Parton RG, McCammon JA, Hancock JF. A novel switch region regulates h-ras membrane orientation and signal output. EMBO J 2008; 27:727-735.
48. Cirstea IC, Gremer L, Dvorsky R, Zhang SC, Piekorz RP, Zenker M, Ahmadian MR. Diverging gain-of-function mechanisms of two novel kras mutations associated with Noonan and cardio-facio-cutaneous syndromes. Human Mol Genet 2013; 22:262-270.
49. Prakash P, Sayyed-Ahmad A, Gorfe AA. The role of conserved waters in conformational transitions of q61h k-ras. PLoS Comput Biol 2012; 8:e100239402
50. Yang MH, Nickerson S, Kim ET, Liot C, Laurent G, Spang R, Philips MR, Shan Y, Shaw DE, Bar-Sagi D, Haigis MC, Haigis KM. Regulation of ras oncogenicity by acetylation. Proc Natl Acad Sci 2012; 109:10843-10848.