Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 2000 Jan;9(1):138–144. doi: 10.1110/ps.9.1.138

Anti-HIV and anti-tumor protein MAP30, a 30 kDa single-strand type-I RIP, shares similar secondary structure and beta-sheet topology with the A chain of ricin, a type-II RIP.

Y X Wang 1, J Jacob 1, P T Wingfield 1, I Palmer 1, S J Stahl 1, J D Kaufman 1, P L Huang 1, P L Huang 1, S Lee-Huang 1, D A Torchia 1
PMCID: PMC2144446  PMID: 10739256

Abstract

MAP30 is a 30 kDa single-stranded, type-I ribosome inactivating protein (RIP) possessing anti-tumor and anti-HIV activities. It binds both ribosomal RNA and the HIV-1 long-terminal repeat DNA. To understand the structural basis for MAP30 activities, we undertook the study of MAP30 by solution NMR spectroscopy. We report nearly complete 1H, 13C, and 15N chemical shift assignments of its 263 amino acids. Based upon an analysis of secondary 13C chemical shifts, 3J(HNHA) coupling constants, hydrogen exchange data, and nuclear Overhauser effect patterns, we find that the secondary structure and beta-sheet topology of MAP30 are very similar to those of the ricin A chain, a subunit of the well-known type-II RIP, even though two proteins display distinct activities. We therefore suggest that MAP30 and ricin A chain share a similar three-dimensional fold, and that the reported functional differences between two proteins arise primarily from differences in local three-dimensional structure and other structural properties such as surface electrostatic potentials.

Full Text

The Full Text of this article is available as a PDF (536.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barbieri L., Battelli M. G., Stirpe F. Ribosome-inactivating proteins from plants. Biochim Biophys Acta. 1993 Dec 21;1154(3-4):237–282. doi: 10.1016/0304-4157(93)90002-6. [DOI] [PubMed] [Google Scholar]
  2. Grzesiek S., Bax A. Amino acid type determination in the sequential assignment procedure of uniformly 13C/15N-enriched proteins. J Biomol NMR. 1993 Mar;3(2):185–204. doi: 10.1007/BF00178261. [DOI] [PubMed] [Google Scholar]
  3. Lee-Huang S., Huang P. L., Chen H. C., Huang P. L., Bourinbaiar A., Huang H. I., Kung H. F. Anti-HIV and anti-tumor activities of recombinant MAP30 from bitter melon. Gene. 1995 Aug 19;161(2):151–156. doi: 10.1016/0378-1119(95)00186-a. [DOI] [PubMed] [Google Scholar]
  4. Lee-Huang S., Huang P. L., Huang P. L., Bourinbaiar A. S., Chen H. C., Kung H. F. Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8818–8822. doi: 10.1073/pnas.92.19.8818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Lee-Huang S., Huang P. L., Nara P. L., Chen H. C., Kung H. F., Huang P., Huang H. I., Huang P. L. MAP 30: a new inhibitor of HIV-1 infection and replication. FEBS Lett. 1990 Oct 15;272(1-2):12–18. doi: 10.1016/0014-5793(90)80438-o. [DOI] [PubMed] [Google Scholar]
  6. Lee-Huang S., Kung H. F., Huang P. L., Bourinbaiar A. S., Morell J. L., Brown J. H., Huang P. L., Tsai W. P., Chen A. Y., Huang H. I. Human immunodeficiency virus type 1 (HIV-1) inhibition, DNA-binding, RNA-binding, and ribosome inactivation activities in the N-terminal segments of the plant anti-HIV protein GAP31. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12208–12212. doi: 10.1073/pnas.91.25.12208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lee-Huang S., Kung H. F., Huang P. L., Huang P. L., Li B. Q., Huang P., Huang H. I., Chen H. C. A new class of anti-HIV agents: GAP31, DAPs 30 and 32. FEBS Lett. 1991 Oct 7;291(1):139–144. doi: 10.1016/0014-5793(91)81122-o. [DOI] [PubMed] [Google Scholar]
  8. Mlsna D., Monzingo A. F., Katzin B. J., Ernst S., Robertus J. D. Structure of recombinant ricin A chain at 2.3 A. Protein Sci. 1993 Mar;2(3):429–435. doi: 10.1002/pro.5560020315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Tumer N. E., Hwang D. J., Bonness M. C-terminal deletion mutant of pokeweed antiviral protein inhibits viral infection but does not depurinate host ribosomes. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3866–3871. doi: 10.1073/pnas.94.8.3866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Wang Y. X., Jacob J., Cordier F., Wingfield P., Stahl S. J., Lee-Huang S., Torchia D., Grzesiek S., Bax A. Measurement of 3hJNC' connectivities across hydrogen bonds in a 30 kDa protein. J Biomol NMR. 1999 Jun;14(2):181–184. doi: 10.1023/a:1008346517302. [DOI] [PubMed] [Google Scholar]
  11. Wang Y. X., Neamati N., Jacob J., Palmer I., Stahl S. J., Kaufman J. D., Huang P. L., Huang P. L., Winslow H. E., Pommier Y. Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell. 1999 Nov 12;99(4):433–442. doi: 10.1016/s0092-8674(00)81529-9. [DOI] [PubMed] [Google Scholar]
  12. Wishart D. S., Bigam C. G., Holm A., Hodges R. S., Sykes B. D. 1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects. J Biomol NMR. 1995 Jan;5(1):67–81. doi: 10.1007/BF00227471. [DOI] [PubMed] [Google Scholar]
  13. Zarling J. M., Moran P. A., Haffar O., Sias J., Richman D. D., Spina C. A., Myers D. E., Kuebelbeck V., Ledbetter J. A., Uckun F. M. Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+ cells by monoclonal antibodies. Nature. 1990 Sep 6;347(6288):92–95. doi: 10.1038/347092a0. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES