Share This Article:

Do membrane proteins cluster without binding between molecules?

DOI: 10.4236/oji.2012.21001    3,424 Downloads   6,973 Views  

ABSTRACT

Clustering is a basic event for the initiation of immune cell responses, and simulation analyses of clustering of membrane proteins have been performed. It was claimed that a cluster is formed by the self-assembly induced by protein dimerization with a high binding speed (Woolf and Linderman, Biophys. Chem. 104, 217-227, 2003). We examined the cluster formation with Monte Carlo simulation using two algorithms. The first was that simulation processes were divided into two substeps. All proteins were subjected to movement in the first substep, followed by reaction in the second substep. The second algorithm was that proteins were first selected to react and proteins which did not react were subjected to movement. The self-assembly induced by dimerization was simulated only with the second algorithm. In this algorithm, monomers dissociated from dimers do not move because these monomers are not selected for movement, and a large proportion of such monomers are selected to form dimers in the next step. The self-assembly was again simulated with the first algorithm containing the conditions that monomers dissociated from dimers did not move in the next movement substep. This algorithm seems to be far removed from natural conditions. Thus, it is inferred that the self-assembly induced by dimerization is unlikely in situ, and that some interaction between proteins is required for cluster formation. In contrast to algorithms in previous simulations, our results suggest that it is more appropriate that proteins move to the same direction for a while and reflect when the collision occurs.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Wang, X. , Fukamachi, T. , Saito, H. and Kobayashi, H. (2012) Do membrane proteins cluster without binding between molecules?. Open Journal of Immunology, 2, 1-8. doi: 10.4236/oji.2012.21001.

References

[1] Horejsi, V. (2003) The roles of membrane microdomains (rafts) in T cell activation. Immunological Reviews, 191, 148-164. doi:10.1034/j.1600-065X.2003.00001.x
[2] Luna, E.J. and Hitt, A.L. (1992) Cytoskeleton-plasma membrane interactions. Science, 258, 955-964. doi:10.1126/science.1439807
[3] Zacharias, D.A., Violin, J.D., Newton, A.C. and Tsien, Y.R. (2002) Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science, 296, 913-916. doi:10.1126/science.1068539
[4] Sharma, P., Varma, R., Sarasij, R.C., Ira, Gousset, K., Krishnamoorthy, G.G., Rao, M. and Mayor, S. (2004) Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell, 116, 577-589. doi:10.1016/S0092-8674(04)00167-9
[5] Leksa, V., Godar, S., Schiller, H.B., Fuertbauer, E., Muhammad, A., Slezakova, K., Horejsi, V., Steinlein, P., Weidle, U.H., Binder, B.R. and Stockinger, H. (2005) TGF-beta-induced apoptosis in endothelial cells mediated by M6P/ IGFII-R and mini-plasminogen. Journal of Cell Science, 118, 4577-4586. doi:10.1242/jcs.02587
[6] Simons, K. and Ikonen, E. (1997) Functional rafts in cell membranes. Nature, 387, 569-572. doi:10.1038/42408
[7] Rietveld, A. and Simons, K. (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochimica et Biophysica Acta, 1376, 467-479.
[8] Lillemeier, B.F., Pfeiffer, J.R., Surviladze, Z., Wilson, B.S. and Davis, M.M. (2006) Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. Proceedings of the National Academy of Sciences of the United States of America, 103, 18992-18997. doi:10.1073/pnas.0609009103
[9] Smith-Garvin, J.E., Koretzky, G.A. and Jordan, M.S. (2009) T cell activation. Annual Review of Immunology, 27, 591-619. doi:10.1146/annurev.immunol.021908.132706
[10] Molnar, E., Dopfer, E.P., Deswal, S. and Schamel, W.W. (2009) Models of antigen receptor activation in the design of vaccines. Current Pharmaceutical Design, 15, 3237- 3248. doi:10.2174/138161209789105216
[11] Molnar, E., Deswal, S. and Schamel, W.W. (2010) Preclustered TCR complexes. FEBS Letters, 584, 4832-4837. doi:10.1016/j.febslet.2010.09.004
[12] Schamel, W.W., Arechaga, I., Risueno, R.M., van Santen, H.M., Cabezas, P., et al. (2005) Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response. The Journal of Experimental Medicine, 202, 493-503. doi:10.1084/jem.20042155
[13] Wilson, B.S., Pfeiffer, J.R., Surviladze, Z., Gaudet, E.A. and Oliver, J.M. (2001) High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc(epsilon)RI and LAT. The Journal of Cell Biology, 154, 645-658. doi:10.1083/jcb.200104049
[14] Lillemeier, B.F., Mortelmaier, M.A., Forstner, M.B., Huppa, J.B., Groves, J.T., et al. (2010) TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation. Nature Immunology, 11, 90-96. doi:10.1038/ni.1832
[15] Sanchez-Lockhart, M. and Miller, J. (2006) Engagement of CD28 outside of the immunological synapse results in up-regulation of IL-2 mRNA stability but not IL-2 transcription. The Journal of Immunology, 176, 4778-4784.
[16] Kobayashi, H., Azuma, R. and Yasunaga, T. (2009) Expression of excess receptors and negative feedback control of signal pathways are required for rapid activation and prompt cessation of signal transduction. Cell Communication and Signaling, 7, 3. doi:10.1186/1478-811X-7-3
[17] Woolf, P.J. and Linderman, J.J. (2003) Self organization of membrane proteins via dimerization. Biophysical Chemistry, 104, 217-227. doi:10.1016/S0301-4622(02)00369-1
[18] Brinkerhoff, C.J., Woold, P.J. and Linderman, J.J. (2004) Monte Carlo simulations of receptor dynamics: insights into cell signaling. Journal of Molecular Histology, 35, 667-677.

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.