Attachment of C-Terminus of SDF-1 Enhances the Biological Activity of Its N-Terminal Peptide

1999 ◽  
Vol 264 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Jiansong Luo ◽  
Zhaowen Luo ◽  
Naiming Zhou ◽  
James W Hall ◽  
Ziwei Huang
Keyword(s):  
Biological Activity ◽  
C Terminus

scholarly journals A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity.

1993 ◽  
Vol 13 (8) ◽  
pp. 4588-4599 ◽  
Author(s):  
E Zacksenhaus ◽  
R Bremner ◽  
R A Phillips ◽  
B L Gallie
Keyword(s):  
Biological Activity ◽  
Transcription Factors ◽  
Gene Product ◽  
Nuclear Localization ◽  
Simian Virus 40 ◽  
T Antigen ◽  
Retinoblastoma Gene ◽  
C Terminus ◽  
Retinoblastoma Gene Product ◽  
Cellular Transcription

The retinoblastoma gene product, p110RB1, appears to regulate cell growth by modulating the activities of nuclear transcription factors. The elements that specify the transport of p110RB1 into the nucleus have not yet been explored. We now report the identification of a basic region, KRSAEGGNPPKPLKKLR, in the C terminus of p110RB1, which has sequence similarity to known bipartite nuclear localization signals (NLSs). A two-amino-acid mutation introduced into this putative NLS [to give mutant NLS(NQ)] or deletion of the entire NLS (delta NLS) abrogated exclusive nuclear localization, yielding proteins which were distributed either equally throughout the cell or predominantly in the cytoplasm. A mutant protein [NLS(NQ)/delta 22] containing both the mutated NLS and a deletion of exon 22, previously shown to disrupt the interaction of p110RB1 with several cellular transcription factors and oncoproteins, accumulated only in the cytoplasm. When fused to the C terminus of Escherichia coli beta-galactosidase, the RB1 NLS directed this protein to the nucleus, indicating that the motif is not only necessary but also sufficient for nuclear transport. Neither NLS(NQ) nor delta NLS was hyperphosphorylated in vivo, but both retained their abilities to interact, in vitro, with simian virus 40 large T antigen, adenovirus E1a, and the cellular transcription factor E2F. When transfected at multiple copy number, the NLS mutant alleles displayed reduced biological activity, measured by inhibition of growth of the osteogenic sarcoma cell line Saos-2, which has no wild-type RB1. Naturally occurring mutations and deletions in exon 25 of RB1 which disrupt the NLS may lead to partial or complete inactivation of p110RB1 and may be responsible for some retinoblastoma and other tumors.

scholarly journals Biological activity of the growth factor-induced cytokine N51: structure-function analysis using N51/Interleukin-8 chimeric molecules.

1994 ◽  
Vol 14 (5) ◽  
pp. 2849-2861 ◽  
Author(s):  
J N Heinrich ◽  
E C O'Rourke ◽  
L Chen ◽  
H Gray ◽  
K S Dorfman ◽  
...  
Keyword(s):  
Biological Activity ◽  
Function Analysis ◽  
Specific Binding ◽  
Biological Activities ◽  
Interleukin 8 ◽  
Early Gene ◽  
Human Neutrophils ◽  
Apparent Homogeneity ◽  
C Terminus ◽  
Hybrid Molecules

The immediate-early gene N51/KC encodes a protein which following expression in the baculovirus system and purification to apparent homogeneity is able to induce chemotaxis and intracellular Ca2+ flux, to compete for 125I-labeled interleukin-8 (IL-8) binding, and upon iodination, to bind specifically to human neutrophils. The activity of N51/KC can be distinguished from that of IL-8 by a number of criteria. First, at equivalent concentrations, the specific binding of [125I]N51/KC to human neutrophils is about 10 times less than that of [125I]IL-8. Second, the competition studies of [125I]IL-8 with IL-8 define a single class of high-affinity receptors, while the presence of both a high- and a low-affinity class of receptors is defined by N51/KC. Third, although the changes in intracellular Ca2+ of fura-2/AM-preloaded human neutrophils elicited by N51/KC and IL-8 are similar, pretreatment of the cells with N51/KC did not result in a loss of response to a subsequent treatment with IL-8; in contrast, treatment with IL-8 did result in the subsequent desensitization to N51/KC. To further characterize N51/KC, mutants and hybrids of N51/KC and IL-8 were produced and analyzed for the ability to compete for [125I]IL-8 binding and elicit intracellular Ca2+ changes in human neutrophils. Two important observations came from these studies. First, the N51/IL-8I hybrid in which the N51/KC sequence between cysteines 2 and 3 (or first disulfide bond) is replaced by the corresponding sequence in IL-8 shows IL-8-like properties, indicating that this region is important for specific receptor recognition. Second, the N51 delta III and IL-8 delta III C-terminus deletion mutants were biologically inactive, but the hybrid molecules N51/IL-8III and IL-8/N51III, in which the C termini were exchanged, had biological activities similar to that of the wild-type molecules, demonstrating that the presence of the C terminus is essential for the biological activity of these chemokines but does not confer receptor specificity.

scholarly journals The C-Terminal Region of Bacteroides fragilis Toxin Is Essential to Its Biological Activity

2006 ◽  
Vol 74 (10) ◽  
pp. 5595-5601 ◽  
Author(s):  
Cynthia L. Sears ◽  
Simy L. Buckwold ◽  
Jai W. Shin ◽  
Augusto A. Franco
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Point Mutations ◽  
Bacteroides Fragilis ◽  
Terminal Region ◽  
Site Directed Mutagenesis ◽  
Amino Acid Residues ◽  
Wild Type ◽  
Reverse Transcription Pcr ◽  
C Terminus

ABSTRACT To evaluate the role of the C-terminal region in Bacteroides fragilis toxin (BFT) activity, processing, and secretion, sequential C-terminal truncation and point mutations were created by site-directed mutagenesis. Determination of BFT activity on HT29/C1 cells, cleavage of E-cadherin, and the capacity to induce interleukin-8 secretion by wild-type BFT and C-terminal deletion mutants showed that deletion of only 2 amino acid residues at the C terminus significantly reduced BFT biological activity and deletion of eight or more amino acid residues obliterated BFT biologic activity. Western blot and reverse transcription-PCR analyses indicated that BFT mutants lacking seven or fewer amino acid residues in the C-terminal region are processed and expressed similar to wild-type BFT. However, BFT mutants lacking eight or more amino acids at the C terminus are expressed similar to wild-type BFT but are unstable. We concluded that the C terminus of BFT is not tolerant of modest amino acid deletions, suggesting that it is biologically important for BFT activity.

scholarly journals Prenylation of mammalian Ras protein in Xenopus oocytes.

1990 ◽  
Vol 10 (11) ◽  
pp. 5945-5949 ◽  
Author(s):  
R Kim ◽  
J Rine ◽  
S H Kim
Keyword(s):  
Biological Activity ◽  
Posttranslational Modification ◽  
Xenopus Oocytes ◽  
Cholesterol Biosynthesis ◽  
Mevalonic Acid ◽  
Xenopus Laevis Oocytes ◽  
Ras Protein ◽  
C Terminus

Ras protein requires an intermediate of the cholesterol biosynthetic pathway for posttranslational modification and membrane anchorage. This step is necessary for biological activity. Maturation of Xenopus laevis oocytes induced by an oncogenic human Ras protein can be inhibited by lovastatin or compactin, inhibitors of the synthesis of mevalonate, an intermediate of cholesterol biosynthesis. This inhibition can be overcome by mevalonic acid or farnesyl diphosphate, a cholesterol biosynthetic intermediate downstream of mevalonate, but not by squalene, an intermediate after farnesyl pyrophosphate in the pathway. This study supports the idea that in Xenopus oocytes, the Ras protein is modified by a farnesyl moiety or its derivative. Furthermore, an octapeptide with the sequence similar to the C-terminus of the c-H-ras protein inhibits the biological activity of Ras proteins in vivo, suggesting that it competes for the enzyme or enzymes responsible for transferring the isoprenoid moiety (prenylation) in the oocytes. This inhibition of Ras prenylation by the peptide was also observed in vitro, using both Saccharomyces cerevisiae and Xenopus oocyte extracts. These observations show that Xenopus oocytes provide a convenient in vivo system for studies of inhibitors of the posttranslational modification of the Ras protein, especially for inhibitors such as peptides that do not penetrate cell membranes.

scholarly journals C-Terminus Amidation Influences Biological Activity and Membrane Interaction of Maculatin 1.1

2021 ◽  
Vol 120 (3) ◽  
pp. 142a-143a
Author(s):  
Shiying Zhu ◽  
Frances Separovic ◽  
Marc-Antoine Sani
Keyword(s):  
Biological Activity ◽  
Membrane Interaction ◽  
C Terminus

Synthesis and biological activity of adipokinetic hormone analogues modified at the C-terminus

Peptides ◽  
1996 ◽  
Vol 17 (8) ◽  
pp. 1285-1290 ◽  
Author(s):  
Michael J. Lee ◽  
Graham J. Goldsworthy ◽  
Constantine P. Poulos ◽  
Anastasia Velentza
Keyword(s):  
Biological Activity ◽  
Adipokinetic Hormone ◽  
C Terminus

Structural relationships in the two-zinc insulin hexamer

1979 ◽  
Vol 57 (6) ◽  
pp. 469-479 ◽  
Author(s):  
E. J. Dodson ◽  
G. G. Dodson ◽  
D. C. Hodgkin ◽  
C. D. Reynolds
Keyword(s):  
Crystal Structure ◽  
Biological Activity ◽  
Main Chain ◽  
Side Chain ◽  
C Terminus ◽  
Structural Relationships ◽  
N Terminus ◽  
Independent Molecules ◽  
A Chain ◽  
Resolution Data

The refinement of the crystal structure of two-Zn pig insulin using 1.5-Å (1 Å = 0.1 nm) resolution data by Fourier and fast Fourier least-squares methods allows us to make detailed comparisons between the two independent molecules present in the two-Zn insulin dimer and to describe their interactions in the monomer, dimer, and hexamer. The main chain structures for the two molecules agree well except at the N terminus of the A chain and the C terminus of the B chain. The residues along the line of the local two-fold axes, apart from theB25 side chain, conform extremely closely to the two-fold symmetry, although the discrepancies are much more apparent away from this axis. The ability of the insulin molecule to adopt different conformations may be an important factor in the expression of its biological activity.

Sign in / Sign up

Export Citation Format

Share Document