共查询到20条相似文献，搜索用时 31 毫秒
1.
Wenfang Dou Yongmei Xu Vijayakanth Pagadala Lars C. Pedersen Jian Liu 《The Journal of biological chemistry》2015,290(33):20427-20437
Heparan sulfate (HS) is a highly sulfated polysaccharide that plays important physiological roles. The biosynthesis of HS involves a series of enzymes, including glycosyltransferases (or HS polymerase), epimerase, and sulfotransferases. N-Deacetylase/N-Sulfotransferase isoform 1 (NDST-1) is a critical enzyme in this pathway. NDST-1, a bifunctional enzyme, displays N-deacetylase and N-sulfotransferase activities to convert an N-acetylated glucosamine residue to an N-sulfo glucosamine residue. Here, we report the cooperative effects between N-deacetylase and N-sulfotransferase activities. Using baculovirus expression in insect cells, we obtained three recombinant proteins: full-length NDST-1 and the individual N-deacetylase and N-sulfotransferase domains. Structurally defined oligosaccharide substrates were synthesized to test the substrate specificities of the enzymes. We discovered that N-deacetylation is the limiting step and that interplay between the N-sulfotransferase and N-deacetylase accelerates the reaction. Furthermore, combining the individually expressed N-deacetylase and N-sulfotransferase domains produced different sulfation patterns when compared with that made by the NDST-1 enzyme. Our data demonstrate the essential role of domain cooperation within NDST-1 in producing HS with specific domain structures. 相似文献
2.
Maxime Delos François Foulquier Charles Hellec Dorothée Vicogne Alexandre Fifre Mathieu Carpentier Dulce Papy-Garcia Fabrice Allain Agnès Denys 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(7):1644-1655
Background
Heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-O-sulfotransferases (HS3STs) in humans, still it is the rarest modification in HS and its biological function is yet misunderstood. HS3ST2 and HS3ST3B exhibit the same activity in vitro. They are however differently expressed in macrophages depending on cell environment, which suggests that they may be involved in distinct cellular processes. Here, we hypothesized that both isozymes might also display distinct subcellular localizations.Methods
The subcellular distribution of HS3ST2 and HS3ST3B was analysed by using overexpression systems in HeLa cells. The localization of endogenous HS3ST2 was confirmed by immunostaining in primary macrophages.Results
We found that HS3ST3B was only localized in the Golgi apparatus and no difference between full-length enzyme and truncated construct depleted of its catalytic domain was observed. In contrast, HS3ST2 was clearly visualized at the plasma membrane. Its truncated form remained in the Golgi apparatus, meaning that the catalytic domain might support correct addressing of HS3ST2 to cell surface. Moreover, we found a partial co-localization of HS3ST2 with syndecan-2 in HeLa cells and primary macrophages. Silencing the expression of this proteoglycan altered the localization of HS3ST2, which suggests that syndecan-2 is required to address the isozyme outside of the Golgi apparatus.Conclusions
We demonstrated that HS3ST3B is a Golgi-resident isozyme, while HS3ST2 is addressed to the plasma membrane with syndecan-2.General significance
The membrane localization of HS3ST2 suggests that this enzyme may participate in discrete processes that occur at the cell surface. 相似文献3.
Ryuta Tobe Hisaaki Mihara 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2433-2440
Background
Selenophosphate, the key selenium donor for the synthesis of selenoprotein and selenium-modified tRNA, is produced by selenophosphate synthetase (SPS) from ATP, selenide, and H2O. Although free selenide can be used as the in vitro selenium substrate for selenophosphate synthesis, the precise physiological system that donates in vivo selenium substrate to SPS has not yet been characterized completely.Scope of review
In this review, we discuss selenium metabolism with respect to the delivery of selenium to SPS in selenoprotein biosynthesis.Major conclusions
Glutathione, selenocysteine lyase, cysteine desulfurase, and selenium-binding proteins are the candidates of selenium delivery system to SPS. The thioredoxin system is also implicated in the selenium delivery to SPS in Escherichia coli.General significance
Selenium delivered via a protein-bound selenopersulfide intermediate emerges as a central element not only in achieving specific selenoprotein biosynthesis but also in preventing the occurrence of toxic free selenide in the cell. This article is part of a Special Issue entitled “Selenium research in biochemistry and biophysics – 200 year anniversary”. 相似文献4.
Tie-Jun Chen Zhe Chi Hong Jiang Guang-Lei Liu Zhong Hu Zhen-Ming Chi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(6):1516-1526
Background
Pullulan and glycogen have many applications and physiological functions. However, to date, it has been unknown where and how the pullulan is synthesized in the yeast cells and if cell wall structure of the producer can affect pullulan and glycogen biosynthesis.Methods
The genes related to cell wall integrity were cloned, characterized, deleted and complemented. The cell wall integrity, pullulan biosynthesis, glycogen accumulation and gene expression were examined.Results
In this study, the GT6 and GT7 genes encoding different α1,2 mannosyltransferases in Aureobasidium melanogenum P16 were cloned and characterized. The proteins deduced from both the GT6 and GT7 genes contained the conserved sequences YNMCHFWSNFEI and YSTCHFWSNFEI of a Ktr mannosyltransferase family. The removal of each gene and both the two genes caused the changes in colony and cell morphology and enhanced glycogen accumulation, leading to a reduced pullulan biosynthesis and the declined expression of many genes related to pullulan biosynthesis. The swollen cells of the disruptants were due to increased accumulation of glycogen, suggesting that uridine diphosphate glucose (UDP-glucose) was channeled to glycogen biosynthesis in the disruptants, rather than pullulan biosynthesis. Complementation of the GT6 and GT7 genes in the corresponding disruptants and growth of the disruptants in the presence of 0.6?M KCl made pullulan biosynthesis, glycogen accumulation, colony and cell morphology be restored.General significance
This is the first report that the two α1,2 mannosyltransferases were required for colony and cell morphology, glycogen accumulation and pullulan biosynthesis in the pullulan producing yeast. 相似文献5.
Tae Sup Lee Young Kim Weiqi Zhang In Ho Song Ching-Hsuan Tung 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(5):1091-1100
Background
Exosomes are nano-sized vesicles derived from the fusion of multivesicular bodies with the surrounding plasma membrane. Exosomes have various diagnostic and therapeutic potentials in cancer and other diseases, thus tracking exosomes is an important issue.Methods
Here, we report a facile exosome labeling strategy using a natural metabolic incorporation of an azido-sugar into the glycan, and a strain-promoted azide-alkyne click reaction. In culture, tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) was spontaneously incorporated into glycans within the cells and later redistributed onto their exosomes. These azido-containing exosomes were then labeled with azadibenzylcyclooctyne (ADIBO)-fluorescent dyes by a bioorthogonal click reaction.Results
Cellular uptake and the in vivo tracking of fluorescent labeled exosomes were evaluated in various cells and tumor bearing mice. Highly metastatic cancer-derived exosomes showed an increased self-homing in vitro and selective organ distribution in vivo.Conclusion
Our metabolic exosome labeling strategy could be a promising tool in studying the biology and distribution of exosomes, and optimizing exosome based therapeutic approaches.General significant
A facile and effective exosome labeling strategy was introduced by presenting azido moiety on the surface of exosome through metabolic glycan synthesis, and then conjugating a strain-promoted fluorescent dye. 相似文献6.
Hyeonjun Kim Hyejin Kim Jeong K. Lee 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2674-2687
Background
Protoporphyrin IX (PPn), an intermediate in the heme biosynthesis reaction, generates singlet oxygen upon exposure to UV light. It has been proposed that PPn is channeled directly to ferrochelatase within a protoporphyrinogen dehydrogenase (PgdH1)-protoporphyrin ferrochelatase (PpfC) complex as a way to avoid this damaging side reaction. However, the PgdH1-PpfC complex has not been characterized, and the question of how heme affects the activities of PgdH1 has not been addressed.Methods
Protein interactions were explored through pull-down assays and western blotting, and the importance of this complex in vivo was examined using inter-species combinations of the two proteins. The purified PgdH1-PpfC complex was characterized kinetically and used for heme binding studies.Results
In Vibrio vulnificus, PgdH1 and PpfC formed an 8:8 heterohexadecameric complex that was important for maintaining PPn at low levels. PpfC catalyzed PPn efficiently whether or not it was part of the complex. Notably, heme was a noncompetitive inhibitor of V. vulnificus PgdH1, but a competitive inhibitor of the human protoporphyrinogen oxidase PgoX.Conclusion
The PdgH1-PpfC complex is important for protective channeling of PPn and for efficient catalysis of free PPn. The production of PPn by PgdH1 is regulated by feedback inhibition by heme.General significance
Both proteobacteria and eukaryotes have evolved mechanisms to prevent the harmful accumulation of the heme biosynthesis intermediate PPn. The data presented here suggest two previously unknown mechanisms: the channeling of PPn through the PgdH1-PpfC complex, and the direct inhibition of PgdH1 activity (PgoX activity as well) by heme. 相似文献7.
Viktoria Dotz Roosmarijn F.H. Lemmers Karli R. Reiding Agnes L. Hipgrave Ederveen Aloysius G. Lieverse Monique T. Mulder Eric J.G. Sijbrands Manfred Wuhrer Mandy van Hoek 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2613-2622
Background
Little is known about enzymatic N-glycosylation in type 2 diabetes, a common posttranslational modification of proteins influencing their function and integrating genetic and environmental influences. We sought to gain insights into N-glycosylation to uncover yet unexplored pathophysiological mechanisms in type 2 diabetes.Methods
Using a high-throughput MALDI-TOF mass spectrometry method, we measured N-glycans in plasma samples of the DiaGene case-control study (1583 cases and 728 controls). Associations were investigated with logistic regression and adjusted for age, sex, body mass index, high-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol, and smoking. Findings were replicated in a nested replication cohort of 232 cases and 108 controls.Results
Eighteen glycosylation features were significantly associated with type 2 diabetes. Fucosylation and bisection of diantennary glycans were decreased in diabetes (odds ratio (OR)?=?0.81, p?=?1.26E-03, and OR?=?0.87, p?=?2.84E-02, respectively), whereas total and, specifically, alpha2,6-linked sialylation were increased (OR?=?1.38, p?=?9.92E-07, and OR?=?1.40, p?=?5.48E-07). Alpha2,3-linked sialylation of triantennary glycans was decreased (OR?=?0.60, p?=?6.38E-11).Conclusions
While some glycosylation changes were reflective of inflammation, such as increased alpha2,6-linked sialylation, our finding of decreased alpha2,3-linked sialylation in type 2 diabetes patients is contradictory to reports on acute and chronic inflammation. Thus, it might have previously unreported immunological implications in type 2 diabetes.General significance
This study provides new insights into N-glycosylation patterns in type 2 diabetes, which can fuel studies on causal mechanisms and consequences of this complex disease. 相似文献8.
9.
Sophie Debs Amy Cohen Elham Hosseini-Beheshti Giovanna Chimini Nicholas H. Hunt Georges E.R. Grau 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):325-331
Background
Malaria is a serious parasitic infection affecting millions of people worldwide each year. Cerebral malaria is the most severe complication of Plasmodium infections, predominantly affecting children. Extracellular vesicles are essential mediators of intercellular communication and include apoptotic bodies, microvesicles and exosomes. Microvesicle numbers increase during disease pathogenesis and inhibition of their release can prevent brain pathology and mortality.Scope of review
We explore the current knowledge on microvesicles and exosomes in cerebral malaria pathogenesis.Major conclusions
Microvesicles and exosomes are implicated in cerebral malaria pathogenesis, in the modulation of host immunity to Plasmodium, and in cell-cell communication. Blocking their production is protective in models of cerebral malaria, both in vivo and in vitro.General significance
While anti-malarial treatments exist to combat Plasmodium infections, increasing drug resistance presents a major challenge. In order to improve diagnosis and treatment outcomes, further research is required to better appreciate extracellular vesicle involvement in cerebral malaria. 相似文献10.
Dunja Urbančič Anita Kotar Alenka Šmid Marko Jukič Stanislav Gobec Lars-Göran Mårtensson Janez Plavec Irena Mlinarič-Raščan 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):182-190
Background
Methylation driven by thiopurine S-methylatransferase (TPMT) is crucial for deactivation of cytostatic and immunosuppressant thiopurines. Despite its remarkable integration into clinical practice, the endogenous function of TPMT is unknown.Methods
To address the role of TPMT in methylation of selenium compounds, we established the research on saturation transfer difference (STD) and 77Se NMR spectroscopy, fluorescence measurements, as well as computational molecular docking simulations.Results
Using STD NMR spectroscopy and fluorescence measurements of tryptophan residues in TPMT, we determined the binding of selenocysteine (Sec) to human recombinant TPMT. By comparing binding characteristics of Sec in the absence and in the presence of methyl donor, we confirmed S-adenosylmethionine (SAM)-induced conformational changes in TPMT. Molecular docking analysis positioned Sec into the active site of TPMT with orientation relevant for methylation reaction. Se-methylselenocysteine (MeSec), produced in the enzymatic reaction, was detected by 77Se NMR spectroscopy. A direct interaction between Sec and SAM in the active site of rTPMT and the formation of both products, MeSec and S-adenosylhomocysteine, was demonstrated using NMR spectroscopy.Conclusions
The present study provides evidence on in vitro methylation of Sec by rTPMT in a SAM-dependant manner.General significance
Our results suggest novel role of TPMT and demonstrate new insights into enzymatic modifications of the 21st amino acid. 相似文献11.
Beata Gąsowska-Bajger Yuki Nishigaya Krystyna Hirsz-Wiktorzak Anna Rybczyńska Toshimasa Yamazaki Hubert Wojtasek 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(7):1626-1634
Background
A number of compounds, including ascorbic acid, catecholamines, flavonoids, p-diphenols and hydrazine derivatives have been reported to interfere with peroxidase-based medical diagnostic tests (Trinder reaction) but the mechanisms of these effects have not been fully elucidated.Methods
Reactions of bovine myeloperoxidase with o-dianisidine, bovine lactoperoxidase with ABTS and horseradish peroxidase with 4-aminoantipyrine/phenol in the presence of carbidopa, an anti-Parkinsonian drug, and other catechols, including l-dopa, were monitored spectrophotometrically and by measuring hydrogen peroxide consumption.Results
Chromophore formation in all three enzyme/substrate systems was blocked in the presence of carbidopa and other catechols. However, the rates of hydrogen peroxide consumption were not much affected. Irreversible enzyme inhibition was also insignificant.Conclusions
Tested compounds reduced the oxidation products or intermediates of model substrates thus preventing chromophore formation. This interference may affect interpretation of results of diagnostic tests in samples from patients with Parkinson's disease treated with carbidopa and l-dopa.General significance
This mechanism allows prediction of interference in peroxidase-based diagnostic tests for other compounds, including drugs and natural products. 相似文献12.
Sumangala Shetty Paul R. Copeland 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2506-2510
Background
Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec), a process that requires a set of dedicated translation factors. Among the mammalian selenoproteins, Selenoprotein P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires multiple Sec incorporation events.Scope of review
In this review we elaborate on new data and current models that provide insight into how SELENOP is made.Major conclusions
SELENOP synthesis requires a specific set of factors and conditions.General significance
As the key protein required for proper selenium distribution, SELENOP stands out as a lynchpin selenoprotein that is essential for male fertility, proper neurologic function and selenium metabolism. 相似文献13.
Nathalie Vaes Simone L. Schonkeren Erwin Brosens Alexander Koch Conor J. McCann Nikhil Thapar Robert M.W. Hofstra Manon van Engeland Veerle Melotte 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2140-2151
Background
The N-Myc Downstream-Regulated Gene (NDRG) family comprises four members that function in cellular processes like proliferation and differentiation. While NDRG1 and NDRG2 are extensively studied, knowledge regarding NDRG3 and NDRG4, despite its recognition as a well-established early-detection marker for colorectal cancer (Cologuard®), is sparse.Scope of review
To summarize expression, biomarker potential and functional mechanisms of the NDRGs in the developing, mature and cancerous gut, we combine current literature and in silico analyses from the TCGA-database, GTEX Project, E14.5 mouse intestine and enteric neural crest cells, and an RNA-sequencing time-series of human embryonic colonic samples.Major conclusions
This study reveals that all members display a differential expression pattern in the gut and that NDRG1, NDRG2 and NDRG4 (1) can serve as biomarker for colorectal cancer and (2) have tumor suppressive properties mainly affecting cell proliferation and epithelial-mesenchymal transition.General significance
Similar effects of the NDRGs on the key-hallmarks of cancer, could implicate analogous functions in other tissue/cancer types. 相似文献14.
Giulia Tedeschi Edoardo Salladini Carlo Santambrogio Rita Grandori Sonia Longhi Stefania Brocca 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2204-2214
Background
Recent theoretical and computational studies have shown that the charge content and, most importantly, the linear distribution of opposite charges are major determinants of conformational properties of intrinsically disordered proteins (IDPs). Charge segregation in a sequence can be measured through κ, which represents a normalized measure of charge asymmetry. A strong inverse correlation between κ and radius of gyration has been previously demonstrated for two independent sets of permutated IDP sequences.Methods
We used two well-characterized IDPs, namely measles virus NTAIL and Hendra virus PNT4, sharing a very similar fraction of charged residues and net charge per residue, but differing in proline (Pro) content. For each protein, we have rationally designed a low- and a high-κ variant endowed with the highest and the lowest κ values compatible with their natural amino acid composition. Then, the conformational properties of wild-type and κ-variants have been assessed by biochemical and biophysical techniques.Results
We confirmed a direct correlation between κ and protein compaction. The analysis of our original data along with those available from the literature suggests that Pro content may affects the responsiveness to charge clustering.Conclusions
Charge clustering promotes IDP compaction, but the extent of its effects depends on the sequence context. Proline residues seem to play a role contrasting compaction.General significance
These results contribute to the identification of sequence determinants of IDP conformational properties. They may also serve as an asset for rational design of non-natural IDPs with tunable degree of compactness. 相似文献15.
Cinzia Tarsia Alberto Danielli Francesca Florini Paolo Cinelli Stefano Ciurli Barbara Zambelli 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2245-2253
Background
Helicobacter pylori is a bacterium strongly associated with gastric cancer. It thrives in the acidic environment of the gastric niche of large portions of the human population using a unique adaptive mechanism that involves the catalytic activity of the nickel-dependent enzyme urease. Targeting urease represents a key strategy for drug design and H. pylori eradication.Method
Here, we describe a novel method to screen, directly in the cellular environment, urease inhibitors. A ureolytic Escherichia coli strain was engineered by cloning the entire urease operon in an expression plasmid and used to test in-cell urease inhibition with a high-throughput colorimetric assay. A two-plasmid system was further developed to evaluate the ability of small peptides to block the protein interactions that lead to urease maturation.Results
The developed assay is a robust cellular model to test, directly in the cell environment, urease inhibitors. The efficacy of a co-expressed peptide to affect the interaction between UreF and UreD, two accessory proteins necessary for urease activation, was observed. This event involves a process that occurs through folding upon binding, pointing to the importance of intrinsically disordered hot spots in protein interfaces.Conclusions
The developed system allows the concomitant screening of a large number of drug candidates that interfere with the urease activity both at the level of the enzyme catalysis and maturation.General significance
As inhibition of urease has the potential of being a global antibacterial strategy for a large number of infections, this work paves the way for the development of new candidates for antibacterial drugs. 相似文献16.
17.
Kirankumar Katta Lawrence F. Sembajwe Marion Kusche-Gullberg 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(6):1472-1481
Background
Exostosin-1 (EXT1), a member of the EXT protein family, is indispensable for synthesis of heparan sulfate (HS) chains that bind to and modulate the signaling efficiency of numerous growth factor activities. We have previously shown that Ext1 mutated mouse embryonic fibroblasts produce short sulfated HS chains which dramatically influence tumor cell behavior in a 3-dimensional (3D) heterospheroid system composed of tumor cells and fibroblasts.Methods
In this study, we have used both 2D co-culture and 3D heterospheroid models, consisting of human A549 carcinoma cells co-cultured with wild-type or Ext1-mutated mouse embryonic fibroblasts.Results and conclusions
Gene expression profiling of differentially expressed genes in fibroblast/A549 heterospheroids identified P311 as a gene substantially down-regulated in A549 cells co-cultured with Ext1-mutated fibroblasts. In addition, we observed that the Ext1 mutants displayed reduced Tgf-β1 mRNA levels and lower levels of secreted active TGF-β protein. Re-introduction of Ext1 in the Ext1 mutant fibroblasts rescued the levels of Tgf-β1 mRNA, increased the amounts of secreted active TGF-β in these cells, as well as P311 mRNA levels in adjacent A549 cells. Accordingly, small interfering RNAs (siRNAs) against fibroblast Tgf-β1 reduced P311 expression in neighboring A549 tumor cells. Our data raises the possibility that fibroblast Ext1 levels play a role in P311 expression in A549/fibroblast co-culture through TGF-β1.General significance
This study considers a possible novel mechanism of Ext1-regulated heparan sulfate structure in modifying tumor-stroma interactions through altering stromal tgf-ß1 expression. 相似文献18.
Ryota Iino Tatsuya Iida Akihiko Nakamura Ei-ichiro Saita Huijuan You Yasushi Sako 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(2):241-252
Background
Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration.Scope of review
We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems.Major conclusions
Single-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines.General significance
Quantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: “What is life?” This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. 相似文献19.
Shuiliang Shi Brian J. Kelly Congrong Wang Ken Klingler Albert Chan George J. Eckert Stephen B. Trippel 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):567-575
Background
Insulin-like growth factor I (IGF-I) is a key regulator of chondrogenesis, but its therapeutic application to articular cartilage damage is limited by rapid elimination from the repair site. The human IGF-I gene gives rise to three IGF-I propeptides (proIGF-IA, proIGF-IB and proIGF-IC) that are cleaved to create mature IGF-I. In this study, we elucidate the processing of IGF-I precursors by articular chondrocytes, and test the hypotheses that proIGF-I isoforms bind to heparin and regulate articular chondrocyte biosynthesis.Methods
Human IGF-I propeptides and mutants were overexpressed in bovine articular chondrocytes. IGF-I products were characterized by ELISA, western blot and FPLC using a heparin column. The biosynthetic activity of IGF-I products on articular chondrocytes was assayed for DNA and glycosaminoglycan that the cells produced.Results
Secreted IGF-I propeptides stimulated articular chondrocyte biosynthetic activity to the same degree as mature IGF-I. Of the three IGF-I propeptides, only one, proIGF-IA, strongly bound to heparin. Interestingly, heparin binding of proIGF-IA depended on N-glycosylation at Asn92 in the EA peptide. To our knowledge, this is the first demonstration that N-glycosylation determines the binding of a heparin-binding protein to heparin.Conclusion
The biosynthetic and heparin binding abilities of proIGF-IA, coupled with its generation of IGF-I, suggest that proIGF-IA may have therapeutic value for articular cartilage repair.General significance
These data identify human pro-insulin-like growth factor IA as a bifunctional protein. Its combined ability to bind heparin and augment chondrocyte biosynthesis makes it a promising therapeutic agent for cartilage damage due to trauma and osteoarthritis. 相似文献20.
Spencer C. Harris Saravanan Devendran João M.P. Alves Sean M. Mythen Phillip B. Hylemon Jason M. Ridlon 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(3):276-283