A point mutation in the c-myc locus of a Burkitt lymphoma abolishes binding of a nuclear protein

Science ◽  
1988 ◽  
Vol 240 (4860) ◽  
pp. 1776-1780 ◽  
Author(s):  
M Zajac-Kaye ◽  
EP Gelmann ◽  
D Levens
Keyword(s):  
Binding Site ◽  
Point Mutation ◽  
Burkitt Lymphoma ◽  
Nuclear Protein ◽  
Chromosomal Translocation ◽  
Binding Region ◽  
Recognition Sequence ◽  
First Intron ◽  
Lymphoma Line ◽  
Myc Gene

A 20-base pair region in the first intron of the human c-myc gene was identified as the binding site of a nuclear protein. This binding site is mutated in five out of seven Burkitt lymphomas sequenced to date. To investigate the protein-recognition region in greater detail, the abnormal c-myc allele from a Burkitt lymphoma line (PA682) that carries a t(8;22) chromosomal translocation was used. A point mutation in the binding region of the PA682 c-myc DNA abolished binding of this nuclear protein. This protein may be an important factor for control of c-myc expression, and mutations in its recognition sequence may be associated with c-myc activation in many cases of Burkitt lymphoma.

Localization of a Vitronectin Binding Region of Plasminogen Activator Inhibitor-1

1995 ◽  
Vol 73 (05) ◽  
pp. 829-834 ◽  
Author(s):  
Jaya Padmanabhan ◽  
David C Sane
Keyword(s):  
Binding Site ◽  
Plasminogen Activator ◽  
Inhibitory Activity ◽  
Plasminogen Activator Inhibitor ◽  
Structural Homology ◽  
Binding Region ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe PAI-1 binding site for VN was studied using two independent methods. PAI-1 was cleaved by Staph V8 protease, producing 8 fragments, only 2 of which bound to [125I]-VN. These fragments were predicted to overlap between residues 91-130. Since PAI-2 has structural homology to PAI-1, but does not bind to vitronectin, chimeras of PAI-1 and PAI-2 were constructed. Four chimeras, containing PAI-1 residues 1-70,1-105,1-114, and 1-167 were constructed and expressed in vitro. PAI-1, PAI-2, and all of the chimeras retained inhibitory activity for t-PA, but only the chimera containing PAI-1 residues 1-167 formed a complex with VN. Together, these results predict that the VN binding site of PAI-1 is between residues 115-130.

scholarly journals The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Ivan Campeotto ◽  
Francis Galaway ◽  
Shahid Mehmood ◽  
Lea K. Barfod ◽  
Doris Quinkert ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Binding Site ◽  
Structural Information ◽  
Blood Stage ◽  
Site Directed Mutagenesis ◽  
Effective Vaccine ◽  
Binding Region ◽  
Fab Fragment ◽  
Content Type ◽  
Blood Stage Malaria

ABSTRACT Plasmodium falciparum RH5 is a secreted parasite ligand that is essential for erythrocyte invasion through direct interaction with the host erythrocyte receptor basigin. RH5 forms a tripartite complex with two other secreted parasite proteins, CyRPA and RIPR, and is tethered to the surface of the parasite through membrane-anchored P113. Antibodies against RH5, CyRPA, and RIPR can inhibit parasite invasion, suggesting that vaccines containing these three components have the potential to prevent blood-stage malaria. To further explore the role of the P113-RH5 interaction, we selected monoclonal antibodies against P113 that were either inhibitory or noninhibitory for RH5 binding. Using a Fab fragment as a crystallization chaperone, we determined the crystal structure of the RH5 binding region of P113 and showed that it is composed of two domains with structural similarities to rhamnose-binding lectins. We identified the RH5 binding site on P113 by using a combination of hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis. We found that a monoclonal antibody to P113 that bound to this interface and inhibited the RH5-P113 interaction did not inhibit parasite blood-stage growth. These findings provide further structural information on the protein interactions of RH5 and will be helpful in guiding the development of blood-stage malaria vaccines that target RH5. IMPORTANCE Malaria is a deadly infectious disease primarily caused by the parasite Plasmodium falciparum. It remains a major global health problem, and there is no highly effective vaccine. A parasite protein called RH5 is centrally involved in the invasion of host red blood cells, making it—and the other parasite proteins it interacts with—promising vaccine targets. We recently identified a protein called P113 that binds RH5, suggesting that it anchors RH5 to the parasite surface. In this paper, we use structural biology to locate and characterize the RH5 binding region on P113. These findings will be important to guide the development of new antimalarial vaccines to ultimately prevent this disease, which affects some of the poorest people on the planet.

The REB1 site is an essential component of a terminator for RNA polymerase I in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (1) ◽  
pp. 649-658
Author(s):  
W H Lang ◽  
R H Reeder
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase ◽  
Protein Binding ◽  
Binding Site ◽  
Rna Polymerase I ◽  
Recognition Sequence ◽  
Sequence Context ◽  
Yeast Saccharomyces Cerevisiae ◽  
Essential Component ◽  
Polymerase I

We have identified a terminator for transcription by RNA polymerase I in the genes coding for rRNA of the yeast Saccharomyces cerevisiae. The terminator is located 108 bp downstream of the 3' end of the mature 25S rRNA and shares several characteristics with previously studied polymerase I terminators in the vertebrates. For example, the yeast terminator is orientation dependent, is inhibited by its own sequence, and forms RNA 3' ends 17 +/- 2 bp upstream of an essential protein binding site. The recognition sequence for binding of the previously cloned REB1 protein (Q. Ju, B. E. Morrow, and J. R. Warner, Mol. Cell. Biol. 10:5226-5234, 1990) is an essential component of the terminator. In addition, the efficiency of termination depends upon sequence context extending at least 12 bp upstream of the REB1 site.

scholarly journals The short-neurotoxin-binding regions on the α-chain of human and Torpedo californica acetylcholine receptors

1991 ◽  
Vol 274 (3) ◽  
pp. 849-854 ◽  
Author(s):  
K H Ruan ◽  
B G Stiles ◽  
M Z Atassi
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptors ◽  
Binding Activity ◽  
Lower Activity ◽  
Binding Region ◽  
Torpedo Californica ◽  
Binding Regions ◽  
Alpha Bungarotoxin ◽  
Erabutoxin B ◽  
Low Activity

The continuous regions for short-neurotoxin binding on the alpha-chains of Torpedo californica (electric ray) and human acetylcholine receptors (AChR) were localized by reaction of 125I-labelled cobrotoxin (Cot) and erabutoxin b (Eb) with synthetic overlapping peptides spanning the entire extracellular part of the respective alpha-chains. On Torpedo AChR, five Cot-binding regions were found to reside within peptides alpha 1-16, alpha 23-38/alpha 34-49 overlap, alpha 100-115, alpha 122-138 and alpha 194-210. The Eb-binding regions were localized within peptides alpha 23-38/alpha 34-49/alpha 45-60 overlap, alpha 100-115 and alpha 122-138. The main binding activity for both toxins resided within region alpha 122-138. In previous studies we had shown that the binding of long alpha-neurotoxins [alpha-bungarotoxin (Bgt) and cobratoxin (Cbt)] involved the same regions on Torpedo AChR as well as an additional region within residues alpha 182-198. Thus region alpha 182-198, which is the strongest binding region for long neurotoxins on Torpedo AChR, was not a binding region for short neurotoxins. On human AChR, peptide alpha 122-138 possessed the highest activity with both toxins, and lower activity was found in the overlap alpha 23-38/alpha 34-49/alpha 45-60 and in peptide alpha 194-210. In addition, peptides alpha 100-115 and alpha 56-71 showed strong and medium binding activities to Eb, but low activity to Cot, whereas peptide alpha 1-16 exhibited low binding to Cot and no binding to Eb. Comparison with previous studies indicated that, for human AChR, the binding regions of short and long neurotoxins were essentially the same. The finding that the region within residues alpha 122-138 of both human and Torpedo AChR possessed the highest binding activity with short neurotoxins indicated that this region constitutes a universal binding site for long and short neurotoxins on AChR from various species.

Point mutation and DNA amplification studies on ras and myc gene in lung cancer

1992 ◽  
Vol 271 (2) ◽  
pp. 121
Author(s):  
P. Hackman ◽  
K. Husgafvel-Pursiainen ◽  
S. Anttila ◽  
M. Ridanpää ◽  
A. Karjalainen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Point Mutation ◽  
Dna Amplification ◽  
Myc Gene

scholarly journals High-affinity binding site for a specific nuclear protein in the human IgM gene

Nature ◽  
1985 ◽  
Vol 315 (6016) ◽  
pp. 254-254
Author(s):  
L. Hennighausen ◽  
U. Siebenlist ◽  
D. Danner ◽  
P. Leder ◽  
D. Rawlins ◽  
...  
Keyword(s):  
Binding Site ◽  
Nuclear Protein ◽  
Affinity Binding ◽  
High Affinity Binding ◽  
High Affinity ◽  
High Affinity Binding Site ◽  
Specific Nuclear Protein
Sign in / Sign up

Export Citation Format

Share Document