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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2), which is found in seminal plasma, promotes capacitation but inhibits spontaneous acrosome loss in mammalian spermatozoa in vitro. Adenosine, known to modulate the adenylyl cyclase (AC)/cAMP pathway, elicits these same responses whereas FPP + adenosine produces an enhanced response, leading to the hypothesis that FPP and adenosine modulate the same signal transduction pathway but act via different receptors. TCP-11, the product of a t-complex gene, is the putative receptor for FPP: Fab fragments of anti-TCP-11 antibodies have the same effect as FPP on mouse spermatozoa and Gln-FPP, a competitive inhibitor of FPP, also competitively inhibits responses to the Fab fragments. In the present study, specific binding of 3H-FPP to sperm membranes was significantly inhibited by 200 nM Gln-FPP and anti-TCP-11 Fab fragments (1/25 dilution), thus confirming that FPP, Gln-FPP, and Fab fragments compete for the same binding site. In addition, spermatozoa treated with A23187 to induce the acrosome reaction bound significantly less 3H-FPP than untreated cells, suggesting that a large proportion of the FPP binding sites are associated with the acrosomal cap region; TCP-11 is located in this region. In other experiments, 100 nM FPP significantly stimulated cAMP production in mouse sperm membranes, permeabilized cells and intact cells. Furthermore, Gln-FPP inhibited production of cAMP in response to FPP but not to adenosine (10 microM) or its analogue NECA (100 nM), supporting the involvement of two different receptors. Finally, anti-TCP-11 Fab fragments (1/25 dilution) significantly stimulated cAMP production, whereas low Fab (1/200; nonstimulatory when used alone) plus adenosine (10 microM) significantly enhanced the stimulation of capacitation by adenosine. These results support the hypotheses that TCP-11 is the receptor for FPP and that FPP<-->TCP-11 interactions modulate AC/cAMP.
Mol Reprod Dev 1998 Dec
PMID:FPP modulates mammalian sperm function via TCP-11 and the adenylyl cyclase/cAMP pathway. 982 Feb 6

The actins and tubulins are the obligate substrates in vivo of the chaperonin-containing TCP-1 (CCT). The precise elements of recognition between the chaperonin and its substrates remain largely unknown. We have used a solid phase peptide binding assay to screen the human alpha, beta and gamma-tubulin sequences for CCT recognition. Multiple regions seem to be implicated in interactions between tubulins and CCT. These potential CCT-binding sites are highly dispersed throughout the primary sequences of the human tubulins. In addition, using site-directed mutagenesis we assessed the contribution of the selected residues in the C-terminal domain of beta-tubulin to CCT binding. Various hot spots have been identified even though, in each case, their replacement by alanine does not reduce dramatically the total affinity of beta-tubulin for CCT. The CCT-binding information in the tubulins is probably confined to multiple specific regions each having weak or moderate affinity for CCT apical domains. The main binding region seems to be located between residues 263 and 384, but there are no single amino acid residues in this region, which make large contributions to the binding energy, although we have detected a minor contribution by F377. These biochemical results are understandable in the context of our recent structural analysis of CCT-tubulin complexes by cryo-electron microscopy and image reconstruction, which shows that, in one stage of an in vitro binding reaction between apo-CCT and tubulin diluted from guanidinium chloride, ten major, stable contacts between tubulin and CCT are involved. Therefore, specificity is achieved through the co-operation of many specific, albeit weak, interactions.
J Mol Biol 2000 Nov 17
PMID:Defining the eukaryotic cytosolic chaperonin-binding sites in human tubulins. 1107 12

We examined the biogenesis of the von Hippel-Lindau (VHL) tumor suppressor protein (pVHL) in vitro and in vivo. pVHL formed a complex with the cytosolic chaperonin containing TCP-1 (CCT or TRiC) en route to assembly with elongin B/C and the subsequent formation of the VCB-Cul2 ubiquitin ligase. Blocking the interaction of pVHL with elongin B/C resulted in accumulation of pVHL within the CCT complex. pVHL present in purified VHL-CCT complexes, when added to rabbit reticulocyte lysate, proceeded to form VCB and VCB-Cul2. Thus, CCT likely functions, at least in part, by retaining VHL chains pending the availability of elongin B/C for final folding and/or assembly. Tumor-associated mutations within exon II of the VHL syndrome had diverse effects upon the stability and/or function of pVHL-containing complexes. First, a pVHL mutant lacking the entire region encoded by exon II did not bind to CCT and yet could still assemble into complexes with elongin B/C and elongin B/C-Cul2. Second, a number of tumor-derived missense mutations in exon II did not decrease CCT binding, and most had no detectable effect upon VCB-Cul2 assembly. Many exon II mutants, however, were found to be defective in the binding to and subsequent ubiquitination of hypoxia-inducible factor 1alpha (HIF-1alpha), a substrate of the VCB-Cul2 ubiquitin ligase. We conclude that the selection pressure to mutate VHL exon II during tumorigenesis does not relate to loss of CCT binding but may reflect quantitative or qualitative defects in HIF binding and/or in pVHL-dependent ubiquitin ligase activity.
Mol Cell Biol 2002 Mar
PMID:Diverse effects of mutations in exon II of the von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHL-dependent ubiquitin ligase activity. 1186 71

The chaperonin containing TCP-1 (CCT, also known as TRiC) is the only member of the chaperonin family found in the cytosol of eukaryotes. Like other chaperonins, it assists the folding of newly synthesised proteins. It is, however, unique in its specificity towards only a small subset of non-native proteins. We determined two crystal structures of mouse CCTgamma apical domain at 2.2 A and 2.8 A resolution. They reveal a surface patch facing the inside of the torus that is highly evolutionarily conserved and specific for the CCTgamma apical domain. This putative substrate-binding region consists of predominantly positively charged side-chains. It suggests that the specificity of this apical domain towards its substrate, partially folded tubulin, is conferred by polar and electrostatic interactions. The site and nature of substrate interaction are thus profoundly different between CCT and its eubacterial homologue GroEL, consistent with their different functions in general versus specific protein folding assistance.
J Mol Biol 2002 May 17
PMID:Crystal structure of the CCTgamma apical domain: implications for substrate binding to the eukaryotic cytosolic chaperonin. 1208 24

The CYCLOIDEA (CYC) and DICHOTOMA (DICH) genes encode related TCP transcription factors that control floral asymmetry in Antirrhinum majus. Analysis of sequences from relatives of Antirrhinum suggested that CYC and DICH arose from a gene duplication in an ancestor of the tribe Antirrhineae and have subsequently evolved at similar rates. Coding regions outside the conserved functional TCP and R domains differed by numerous indels, suggesting rapid evolution and low constraint on amino acid sequence. An analysis of variability within the genus Antirrhinum revealed very similar CYC alleles in 17 representative species, consistent with most of the species having diverged within the last 1 myr. Whereas substitution mutations appear to have accumulated constantly, one Antirrhinum CYC allele provided evidence for sporadic and rapid accumulation of insertion mutations.
Mol Biol Evol 2003 Sep
PMID:Rapid molecular evolution of CYCLOIDEA-like genes in Antirrhinum and its relatives. 1283 47

In the plant subclass Asteridae, bilaterally symmetrical flowers have evolved from a radially symmetrical ancestral phenotype on at least three independent occasions: in the Boraginaceae, Solanaceae, and Lamiales. Development of bilateral flower symmetry has been shown to be determined by the early-acting cycloidea (cyc) and dichotoma (dich) genes in Antirrhinum, a member of the Lamiales. cyc and dich belong to the TCP gene family of putative transcription factors. TCP gene sequences were isolated from 11 Asteridae taxa using an array of degenerate PCR primers. Closely related species exhibiting either ancestral actinomorphic or derived zygomorphic flowers were sampled for each independent origin of bilateral flower symmetry. Cladistic and network-based analyses were performed to establish viable hypotheses regarding the evolution of bilateral symmetry in Asteridae. For the TCP gene family, the use of cladistic phylogenetic analysis to identify orthologous genes is complicated by a paucity of alignable data, frequent gene duplication and extinction, and the possibility of reticulate evolution via intergenic recombination. These complicating factors can be generalized to many regulatory gene families. As an alternative to cladistic analysis, we propose the use of network analysis for the reconstruction of regulatory gene family phylogenetic and functional relationships. Results of analyses support the hypothesis that the origin of bilaterally symmetrical flowers in the Boraginaceae and Solanaceae did not require orthologs or functional analogs of cyc or dich. This suggests that the genetic mechanism that determines bilateral flower symmetry in these taxa is not homologous to that of the Lamiales. Results of analyses are consistent with the hypothesis that the evolution of bilateral floral symmetry in the Lamiales required the origin of a novel gene function subsequent to gene duplication.
Mol Biol Evol 2003 Dec
PMID:Evolution of the TCP gene family in Asteridae: cladistic and network approaches to understanding regulatory gene family diversification and its impact on morphological evolution. 1288 53

TCP80 is an approximately 80kDa mammalian cytoplasmic protein that binds to a set of mRNAs and inhibits their translation in vitro and ex vivo. This protein has high sequence similarity to interleukin-2 enhancer-binding factors (NF90/ILF3) and the M-phase phosphoprotein (MPP4)/DRBP76. A 110kDa immunologic isoform of TCP80/NF90/MPP4/DRBP76, termed TCP110, also is present in cytoplasm and nuclei of many types of cells. A cDNA sequence coding for TCP110 was derived by 5(')RACE. The TCP110 sequence is identical to ILF3. The gene coding for TCP110/ILF3 mapped to human chromosome 19 and the gene organization was analyzed using TCP80 and TCP110/ILF3 cDNA sequences. The TCP/ILF3 gene spans >34.8kb and contains 21 exons. At least one alternatively spliced product involving exons 19-21 exists and predicts the formation of either TCP80 or TCP110/ILF3. However, the functional relationships of TCP80 and TCP110/ILF3 required elucidation. The metabolic turnover rates and subcellular distribution of TCP80 and TCP110/ILF3 during the cell cycle showed TCP80 to be relatively stable (t(1/2)=5 days) in the cytoplasmic compartment. In comparison, TCP110/ILF3 migrated between the cytoplasmic and nuclear compartments during the cell cycle. The TCP110 C-terminal segment contains an additional nuclear localizing signal that plays a role in its nuclear translocation. This study indicates that the multiple cellular functions, i.e., translation control, interleukin-2 enhancer binding, or cell division, of TCP/ILF3 are fulfilled by alternatively spliced isoforms.
Mol Genet Metab 2003 Dec
PMID:Cell cycle dependent intracellular distribution of two spliced isoforms of TCP/ILF3 proteins. 1465 56

Chaperonins are a family of proteins devoted to assisting the folding of other proteins. They are large oligomers assembled into ring structures that enclose a cavity in which folding takes place. For this process to occur, the chaperonin must first recognize and interact with the unfolded polypeptide, then undergo a conformational change upon nucleotide binding that results in the closure of the cavity which in turn mediates the folding reaction inside the cavity. Although this general mechanism seems to apply to every chaperonin studied so far, there exist two different modes of interaction between the chaperonin and the substrate. The first occurs mainly through the interaction between the exposed hydrophobic residues of the unfolded polypeptides and those of the chaperonin substrate binding site, as elucidated for the chaperonin GroEL from E. coli. The second type of mechanism has been described so far only for the cytosolic chaperonin CCT (Chaperonin Containing TCP-1) and here the interaction seems to be of a more specific nature, involving charged and polar residues in both the chaperonin and the substrate, which interacts with CCT in a structured, quasi-native conformation.
J Mol Recognit
PMID:The substrate recognition mechanisms in chaperonins. 1502 29

Hfq is an RNA-binding protein that interacts with both small untranslated RNAs (sRNAs) and mRNAs to modulate gene expression post-transcriptionally. In Escherichia coli and Salmonella typhimurium, Hfq is required for efficient expression of the stationary phase sigma factor sigma(S), and consequently is critical for Salmonella virulence. We have found that Hfq is also essential for the virulence of Vibrio cholerae, as strains lacking hfq fail to colonize the suckling mouse intestine. Deletion of the V. cholerae hfq does not prevent production of sigma(S), nor does it prevent expression of TCP, V. cholerae's primary colonization factor. The expression and activity of the alternative sigma factor sigma(E) are dramatically increased in a V. cholerae hfq mutant. Comparison of the transcriptome of an hfq mutant with that of an rseA mutant, which also overexpresses sigma(E), revealed that sigma(E) controls approximately half the genes found to be upregulated in the hfq mutant. However, increased sigma(E) does not appear to account for this strain's reduced virulence. It is likely that sRNAs, in conjunction with Hfq, are critical regulators of V. cholerae pathogenicity.
Mol Microbiol 2004 Jul
PMID:Hfq is essential for Vibrio cholerae virulence and downregulates sigma expression. 1522 27

In this paper we present the expandability and flexibility features of the VEGA program (downloadable free of charge at http://www.ddl.unimi.it), for the development of custom applications, using it as a multipurpose graphical environment. VEGA can be customized using both plug-in architecture and script programming. The first is useful to add new features and functions, using homemade routines, written with the VEGA Plug-in Development Kit (SDK). With the second approach it is possible to design scripts in VEGA, using the REBOL language, in order to (1) add new functions or customize existing ones; (2) automate common procedures; and (3) allow network communications, by creating a bridge between VEGA and other applications (or other PCs) through the TCP/IP protocol.
J Comput Aided Mol Des 2004 Mar
PMID:VEGA--an open platform to develop chemo-bio-informatics applications, using plug-in architecture and script programming. 1536 17


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