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Protein Science : a Publication of the... Nov 2023Investigating the evolution of structural features in modern multidomain proteins helps to understand their immense diversity and functional versatility. The class of...
Investigating the evolution of structural features in modern multidomain proteins helps to understand their immense diversity and functional versatility. The class of periplasmic binding proteins (PBPs) offers an opportunity to interrogate one of the main processes driving diversification: the duplication and fusion of protein sequences to generate new architectures. The symmetry of their two-lobed topology, their mechanism of binding, and the organization of their operon structure led to the hypothesis that PBPs arose through a duplication and fusion event of a single common ancestor. To investigate this claim, we set out to reverse the evolutionary process and recreate the structural equivalent of a single-lobed progenitor using ribose-binding protein (RBP) as our model. We found that this modern PBP can be deconstructed into its lobes, producing two proteins that represent possible progenitor halves. The isolated halves of RBP are well folded and monomeric proteins, albeit with a lower thermostability, and do not retain the original binding function. However, the two entities readily form a heterodimer in vitro and in-cell. The x-ray structure of the heterodimer closely resembles the parental protein. Moreover, the binding function is fully regained upon formation of the heterodimer with a ligand affinity similar to that observed in the modern RBP. This highlights how a duplication event could have given rise to a stable and functional PBP-like fold and provides insights into how more complex functional structures can evolve from simpler molecular components.
Topics: Periplasmic Binding Proteins; Carrier Proteins; Amino Acid Sequence; Ligands; Protein Binding; Evolution, Molecular
PubMed: 37788980
DOI: 10.1002/pro.4793 -
Journal of Biomedicine & Biotechnology 2010Myosin binding protein C (MyBP-C) consists of a family of thick filament associated proteins. Three isoforms of MyBP-C exist in striated muscles: cardiac, slow skeletal,... (Review)
Review
Myosin binding protein C (MyBP-C) consists of a family of thick filament associated proteins. Three isoforms of MyBP-C exist in striated muscles: cardiac, slow skeletal, and fast skeletal. To date, most studies have focused on the cardiac form, due to its direct involvement in the development of hypertrophic cardiomyopathy. Here we focus on the slow skeletal form, discuss past and current literature, and present evidence to support that: (i) MyBP-C slow comprises a subfamily of four proteins, resulting from complex alternative shuffling of the single MyBP-C slow gene, (ii) the four MyBP-C slow isoforms are expressed in variable amounts in different skeletal muscles, (iii) at least one MyBP-C slow isoform is preferentially found at the periphery of M-bands and (iv) the MyBP-C slow subfamily may play important roles in the assembly and stabilization of sarcomeric M- and A-bands and regulate the contractile properties of the actomyosin filaments.
Topics: Animals; Carrier Proteins; Humans; Protein Isoforms
PubMed: 20396395
DOI: 10.1155/2010/652065 -
BMC Veterinary Research Jan 2024Poly C Binding Protein 1 (PCBP1) belongs to the heterogeneous nuclear ribonucleoprotein family. It is a multifunctional protein that participates in several functional...
BACKGROUND
Poly C Binding Protein 1 (PCBP1) belongs to the heterogeneous nuclear ribonucleoprotein family. It is a multifunctional protein that participates in several functional circuits and plays a variety of roles in cellular processes. Although PCBP1 has been identified in several mammals, its function in porcine was unclear.
RESULTS
In this study, we cloned the gene of porcine PCBP1 and analyzed its evolutionary relationships among different species. We found porcine PCBP1 protein sequence was similar to that of other animals. The subcellular localization of PCBP1 in porcine kidney cells 15 (PK-15) cells was analyzed by immunofluorescence assay (IFA) and revealed that PCBP1 was mainly localized to the nucleus. Reverse transcription-quantitative PCR (RT-qPCR) was used to compare PCBP1 mRNA levels in different tissues of 30-day-old pigs. Results indicated that PCBP1 was expressed in various tissues and was most abundant in the liver. Finally, the effects of PCBP1 on cell cycle and apoptosis were investigated following its overexpression or knockdown in PK-15 cells. The findings demonstrated that PCBP1 knockdown arrested cell cycle in G0/G1 phase, and enhanced cell apoptosis.
CONCLUSIONS
Porcine PCBP1 is a highly conserved protein, plays an important role in determining cell fate, and its functions need further study.
Topics: Swine; Animals; Carrier Proteins; RNA-Binding Proteins; DNA-Binding Proteins; Heterogeneous-Nuclear Ribonucleoproteins; Apoptosis; Protein Binding; Mammals
PubMed: 38218813
DOI: 10.1186/s12917-023-03861-4 -
FEBS Letters Sep 2021Substrate-binding proteins (SBPs) mediate ligand translocation and have been classified into seven clusters (A-G). Although the substrate specificities of these clusters...
Substrate-binding proteins (SBPs) mediate ligand translocation and have been classified into seven clusters (A-G). Although the substrate specificities of these clusters are known to some extent, their ligand-binding mechanism(s) remain(s) incompletely understood. In this study, the list of SBPs belonging to different clusters was updated (764 SBPs) compared to the previously reported study (504 SBPs). Furthermore, a new cluster referred to as cluster H was identified. Results reveal that SBPs follow different ligand-binding mechanisms. Intriguingly, the majority of the SBPs follow the 'one domain movement' rather than the well-known 'Venus Fly-trap' mechanism. Moreover, SBPs of a few clusters display subdomain conformational movement rather than the complete movement of the N- and C-terminal domains.
Topics: Carrier Proteins; Databases, Protein; Humans; Ligands; Models, Molecular; Movement; Protein Binding; Protein Domains; Protein Folding; Substrate Specificity
PubMed: 34379808
DOI: 10.1002/1873-3468.14174 -
FEBS Letters Aug 1995A cytosolic 21-23 kDa protein isolated from bovine brain was demonstrated to bind hydrophobic ligands, particularly phosphatidylethanolamine. The protein was encountered... (Review)
Review
A cytosolic 21-23 kDa protein isolated from bovine brain was demonstrated to bind hydrophobic ligands, particularly phosphatidylethanolamine. The protein was encountered in numerous tissues of several species. High expression of the mRNA encoding the 21-23 kDa protein was found in rat testes. Immunohistochemical studies showed the presence of the 21-23 kDa protein in the elongated spermatids and epididymal fluid of rat testis and in brain oligodendrocytes of developing rats. As the bovine, human and rat brain 21-23 kDa proteins had only few sequence homologies with already know proteins, ti was concluded that they belong to a new protein family. In order to get additional information on the structural features of the 21-23 kDa protein, we built a molecular model which displayed a nucleotide binding site. The affinity of the bovine brain 21-23 kDa protein towards nucleotides as well as its association with cytosolic proteins and small GTP-binding proteins were demonstrated. Recently, significant sequence homologies were found with an antigen from Onchocerca volvulus, a fruit fly odorant-binding protein and the yeast protein TFS1 which is a dosage-dependent suppressor of CDC25 mutations. A positive regulation of RAS is carried out by CDC25 product which facilitates the GDP/GTP exchange on RAS proteins. These results imply that 21-23 kDa proteins function in oxidoreduction reactions and signal mechanisms during cell growth and maturation.
Topics: Amino Acid Sequence; Androgen-Binding Protein; Animals; Brain Chemistry; Carrier Proteins; Cytosol; Ligands; Male; Molecular Sequence Data; Nucleotides; Phosphatidylethanolamine Binding Protein; Phospholipid Transfer Proteins; Prostatein; Secretoglobins; Sequence Homology, Amino Acid; Species Specificity; Testis; Tissue Distribution; Uteroglobin
PubMed: 7641877
DOI: 10.1016/0014-5793(95)00376-k -
The Journal of Biological Chemistry Sep 1991A novel Mr 17,000 heparin-binding protein was purified from culture medium conditioned by A431 human epidermoid carcinoma cells. This protein, designated HBp17, was...
A novel Mr 17,000 heparin-binding protein was purified from culture medium conditioned by A431 human epidermoid carcinoma cells. This protein, designated HBp17, was found to bind the heparin-binding peptide growth factors HBGF-1 and HBGF-2 in a noncovalent, reversible manner. In addition HBp17 was found to inhibit the biological activities of both HBGF-1 and HBGF-2. Both the binding and inactivation of HBGF-1 and HBGF-2 by HBp17 were abolished by heparin. Full-length 1163-base pair HBp17 cDNA was cloned and sequenced by using the polymerase chain reaction technique. The deduced primary structure of HBp17 consisted of 234 amino acids including each of five partial peptide sequences obtained from proteolytic fragments of purified HBp17. The encoded protein included a 33-residue N-terminal signal sequence for secretion and a single potential N-linked glycosylation site. No homology with any known protein was found for the deduced primary structure of HBp17. The expression of HBp17 mRNA was found to occur preferentially in normal human keratinocytes and in squamous cell carcinomas. This pattern of HBp17 gene expression suggests that this binding protein for HBGFs 1 and 2 has a physiological role in squamous epithelia.
Topics: Amino Acid Sequence; Base Sequence; Blotting, Northern; Blotting, Western; Carrier Proteins; Chromatography, Affinity; Cloning, Molecular; DNA; Heparin; Humans; Intercellular Signaling Peptides and Proteins; Molecular Sequence Data; Polymerase Chain Reaction; Tumor Cells, Cultured
PubMed: 1885605
DOI: No ID Found -
FEBS Letters Jul 2016Polyglutamine tract-binding protein 1 (PQBP1) is an intrinsically disordered protein composed of a small folded WW domain and a long disordered region. PQBP1 binds to...
Polyglutamine tract-binding protein 1 (PQBP1) is an intrinsically disordered protein composed of a small folded WW domain and a long disordered region. PQBP1 binds to spliceosomal proteins WBP11 and U5-15kD through its N-terminal WW domain and C-terminal region, respectively. Here, we reveal that the binding between PQBP1 and WBP11 reduces the binding affinity between PQBP1 and U5-15kD. Our results suggest that the interaction between PQBP1 and WBP11 negatively modulates the U5-15kD binding of PQBP1 by an allosteric mechanism.
Topics: Allosteric Regulation; Carrier Proteins; DNA-Binding Proteins; Humans; Nuclear Proteins; Protein Binding; Protein Domains; RNA Splicing Factors; Ribonucleoprotein, U5 Small Nuclear
PubMed: 27314904
DOI: 10.1002/1873-3468.12256 -
Cell Chemical Biology Feb 2016The promiscuous functions of proteins are an important reservoir of functional novelty in protein evolution, but the molecular basis for binding promiscuity remains...
The promiscuous functions of proteins are an important reservoir of functional novelty in protein evolution, but the molecular basis for binding promiscuity remains elusive. We used ancestral protein reconstruction to experimentally characterize evolutionary intermediates in the functional expansion of the polar amino acid-binding protein family, which has evolved to bind a variety of amino acids with high affinity and specificity. High-resolution crystal structures of an ancestral arginine-binding protein in complex with l-arginine and l-glutamine show that the promiscuous binding of l-glutamine is enabled by multi-scale conformational plasticity, water-mediated interactions, and selection of an alternative conformational substate productive for l-glutamine binding. Evolution of specialized glutamine-binding proteins from this ancestral protein was achieved by displacement of water molecules from the protein-ligand interface, reducing the entropic penalty associated with the promiscuous interaction. These results provide a structural and thermodynamic basis for the co-option of a promiscuous interaction in the evolution of binding specificity.
Topics: Amino Acids; Binding Sites; Calorimetry; Carrier Proteins; Evolution, Molecular; Ligands; Models, Molecular; Phylogeny; Solubility; Thermodynamics
PubMed: 26853627
DOI: 10.1016/j.chembiol.2015.12.010 -
Scientific Reports Apr 2018The Y-box proteins are multifunctional nucleic acid-binding proteins involved in various aspects of gene regulation. The founding member of the Y-box protein family,...
The Y-box proteins are multifunctional nucleic acid-binding proteins involved in various aspects of gene regulation. The founding member of the Y-box protein family, YB-1, functions as a transcription factor as well as a principal component of messenger ribonucleoprotein particles (mRNPs) in somatic cells. The nuclear level of YB-1 is well correlated with poor prognosis in many human cancers. Previously, we showed that a Y-box protein-associated acidic protein, YBAP1, which is identical to complement component 1, q subcomponent-binding protein (C1QBP, also called gC1qR, hyaluronan-binding protein 1 [HABP1] or ASF/SF2-associated protein p32), relieves translational repression by YB-1. Here we show that the nuclear localization of YB-1 harboring a point mutation in the cold shock domain was inhibited when co-expressed with YBAP1, whereas cytoplasmic accumulation of the wild-type YB-1 was not affected. We showed that YBAP1 inhibited the interaction between YB-1 and transportin 1. In the cytoplasm, YBAP1 affected the accumulation of YB-1 to processing bodies (P-bodies) and partially abrogated the mRNA stabilization by YB-1. Our results, indicating that YBAP1/C1QBP regulates the nucleo-cytoplasmic distribution of YB-1 and its cytoplasmic functions, are consistent with a model that YBAP1/C1QBP acts as an mRNP remodeling factor.
Topics: Carrier Proteins; Cell Nucleus; Cytoplasm; Gene Expression; HeLa Cells; Humans; Mitochondrial Proteins; Models, Biological; Mutation; Protein Binding; Protein Interaction Domains and Motifs; Protein Transport; RNA Stability; RNA, Messenger; Y-Box-Binding Protein 1; beta Karyopherins
PubMed: 29670170
DOI: 10.1038/s41598-018-24401-3 -
FEBS Letters Jun 1997The small GTPase Rho regulates several actomyosin-based cellular processes such as cell adhesion, cytokinesis and contraction. The biochemical mechanisms of these... (Review)
Review
The small GTPase Rho regulates several actomyosin-based cellular processes such as cell adhesion, cytokinesis and contraction. The biochemical mechanisms of these actions remain unknown. Recently, several GTP-Rho binding proteins were isolated. Among them, p140mDia and p160ROCK appear to work as Rho effectors mediating its action on the cytoskeleton. p140mDia induces actin polymerization by recruiting an actin binding protein, profilin, to the site of Rho action. p160ROCK induces focal adhesions and stress fibers by activating integrin and clustering them by the use of myosin-based contractility.
Topics: Actins; Animals; Carrier Proteins; GTP-Binding Proteins; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Models, Biological; Protein Serine-Threonine Kinases; rho-Associated Kinases; rhoB GTP-Binding Protein
PubMed: 9247125
DOI: 10.1016/s0014-5793(97)00317-7