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.
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.
Wang
Y X
YX
Molecular Structural Biology Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Jacob
J
J
Wingfield
P T
PT
Palmer
I
I
Stahl
S J
SJ
Kaufman
J D
JD
Huang
P L
PL
Huang
P L
PL
Lee-Huang
S
S
Torchia
D A
DA
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D054788:Ribosome Inactivating Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000737:chemistry
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; C066347:MAP30 protein, Momordica charantia; D011506:Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin; D054788:Ribosome Inactivating Proteins