Proteoglycan research最新文献

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Interplay of heparan sulfate chains with the core proteins of syndecans 2 and 4 硫酸乙酰肝素链与syndecans 2和4核心蛋白的相互作用
Proteoglycan research Pub Date : 2023-07-01 DOI: 10.1002/pgr2.10
Martyna Maszota‐Zieleniak, Adam Liwo, Sylvie Ricard‐Blum, Sergey A. Samsonov
{"title":"Interplay of heparan sulfate chains with the core proteins of syndecans 2 and 4","authors":"Martyna Maszota‐Zieleniak, Adam Liwo, Sylvie Ricard‐Blum, Sergey A. Samsonov","doi":"10.1002/pgr2.10","DOIUrl":"https://doi.org/10.1002/pgr2.10","url":null,"abstract":"Abstract We have previously shown that the extracellular domains of the four syndecans are intrinsically disordered, and adopt a wide range of conformations. We report here the building of coarse‐grained models of the extracellular domains of human syndecans 2 and 4 using small‐angle X‐ray scattering restraints. One, two or three heparan sulfate (HS) hexadecasaccharides, (IdoA[2S]GlcNS[6S]) 8 , were attached to three serine residues of the core proteins, resulting in eight variants for each syndecan that were used for all‐atom molecular dynamics (MD) simulations (0.5–1 µs). Syndecan‐4 had a larger conformational diversity than syndecan‐2, and remained extended during MD simulations in absence of HS whereas syndecan‐2 adopted more compact conformations. Their core proteins thus appeared to be structurally distinct. The HS chains also behave differently, the middle chain being more flexible in syndecan‐4, and the third chain being able to interact with the core protein regions mediating cell adhesion. The cell adhesion sites on both core proteins were flexible, with or without HS chains, the NXIP motif of syndecan‐2 being located in a particularly flexible region. In conclusion, the HS chains induce moderate changes in the conformational dynamics of both syndecans, depending on the number of HS chains and their location on the core protein, and on the core protein itself.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"728 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136260478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Correction to “Functional and structural insights into human N‐deacetylase/N‐sulfotransferase activities” 对“人类N‐去乙酰酶/N‐硫转移酶活性的功能和结构见解”的更正
Proteoglycan research Pub Date : 2023-07-01 DOI: 10.1002/pgr2.12
{"title":"Correction to “Functional and structural insights into human <i>N</i>‐deacetylase/<i>N</i>‐sulfotransferase activities”","authors":"","doi":"10.1002/pgr2.12","DOIUrl":"https://doi.org/10.1002/pgr2.12","url":null,"abstract":"","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"97 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135857748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of hyperglycemia‐evoked intracellular hyaluronan accumulation and its activity on the autophagic and endoplasmic reticulum stress pathways 高血糖诱发的细胞内透明质酸积累及其在自噬和内质网应激途径中的作用
Proteoglycan research Pub Date : 2023-07-01 DOI: 10.1002/pgr2.7
A. Wang, Aimin Wang, V. Hascall
{"title":"The role of hyperglycemia‐evoked intracellular hyaluronan accumulation and its activity on the autophagic and endoplasmic reticulum stress pathways","authors":"A. Wang, Aimin Wang, V. Hascall","doi":"10.1002/pgr2.7","DOIUrl":"https://doi.org/10.1002/pgr2.7","url":null,"abstract":"","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84421742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional and structural insights into human N‐deacetylase/N‐sulfotransferase activities 人类N -去乙酰化酶/N -硫转移酶活性的功能和结构分析
Proteoglycan research Pub Date : 2023-07-01 DOI: 10.1002/pgr2.8
Sylvain D. Vallet, T. Annaval, R. Vivès, Emeline Richard, Jérôme Hénault, C. Le Narvor, D. Bonnaffé, B. Priem, R. Wild, H. Lortat‐Jacob
{"title":"Functional and structural insights into human N‐deacetylase/N‐sulfotransferase activities","authors":"Sylvain D. Vallet, T. Annaval, R. Vivès, Emeline Richard, Jérôme Hénault, C. Le Narvor, D. Bonnaffé, B. Priem, R. Wild, H. Lortat‐Jacob","doi":"10.1002/pgr2.8","DOIUrl":"https://doi.org/10.1002/pgr2.8","url":null,"abstract":"Heparan sulfate (HS) is a linear polysaccharide composed of a glucuronic acid (GlcA)‐N‐acetyl‐glucosamine (GlcNAc) disaccharide repeat motif, polymerized by the EXT1–EXT2 complex. It is extensively modified by a series of Golgi localized enzymes, that generate distinct saccharide sequences involved in the binding and the regulation of numerous protein partners. N‐deacetylase/N‐sulfotransferase (NDST), of which four isoforms have been identified in mammals, are involved in the first step of this process and catalyze both the N‐deacetylation of the GlcNAc residues into GlcNH2 and its re‐N‐sulfation into GlcNS residues. Further modifications of the HS chain depend on this first maturation event, NDST action is, therefore, key to HS biosynthesis. However, although the sulfotransferase domain of NDST1 has been characterized at the structural level some 20 years ago, information on the overall structure and activity of the enzyme are still lacking. Here, we report the characterization of the two most expressed NDSTs in humans, NDST1 and NDST2, and a model structure of NDST1 homodimer using cryoelectron microscopy combined with AlphaFold2 modeling. Structure‐driven mutagenesis along with two bioassays to follow the protein activities allowed us to characterize the kinetics of the deacetylation and sulfoaddition and to identify the residue H529 as necessary for N‐deacetylation. These results shed light on a poorly understood family of enzymes and will help deciphering the molecular basis for HS and heparin maturation.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87913298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glypicans, 35 years later 35年后的古希腊人
Proteoglycan research Pub Date : 2023-04-01 DOI: 10.1002/pgr2.5
J. Filmus
{"title":"Glypicans, 35 years later","authors":"J. Filmus","doi":"10.1002/pgr2.5","DOIUrl":"https://doi.org/10.1002/pgr2.5","url":null,"abstract":"","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"152 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85389021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Functional organization of extracellular hyaluronan, CD44, and RHAMM 细胞外透明质酸、CD44和RHAMM的功能组织
Proteoglycan research Pub Date : 2023-04-01 DOI: 10.1002/pgr2.4
M. Cowman, E. Turley
{"title":"Functional organization of extracellular hyaluronan, CD44, and RHAMM","authors":"M. Cowman, E. Turley","doi":"10.1002/pgr2.4","DOIUrl":"https://doi.org/10.1002/pgr2.4","url":null,"abstract":"","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"171 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76612066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
The centrality of proteoglycan research: Expect the unexpected 蛋白聚糖研究的中心地位:期待意外
Proteoglycan research Pub Date : 2023-01-01 DOI: 10.1002/pgr2.2
R. Iozzo
{"title":"The centrality of proteoglycan research: Expect the unexpected","authors":"R. Iozzo","doi":"10.1002/pgr2.2","DOIUrl":"https://doi.org/10.1002/pgr2.2","url":null,"abstract":"","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75813250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular vesicles released during hypoxia transport heparanase and enhance macrophage migration, endothelial tube formation and cancer cell stemness. 缺氧时释放的细胞外囊泡可运输肝素酶,并增强巨噬细胞迁移、内皮管形成和癌细胞干性。
Proteoglycan research Pub Date : 2023-01-01 Epub Date: 2023-03-28 DOI: 10.1002/pgr2.1
Kaushlendra Tripathi, Shyam K Bandari, Ralph D Sanderson
{"title":"Extracellular vesicles released during hypoxia transport heparanase and enhance macrophage migration, endothelial tube formation and cancer cell stemness.","authors":"Kaushlendra Tripathi, Shyam K Bandari, Ralph D Sanderson","doi":"10.1002/pgr2.1","DOIUrl":"10.1002/pgr2.1","url":null,"abstract":"<p><p>Heparanase is upregulated during the progression of most cancers and via its enzyme activity promotes extracellular matrix degradation, angiogenesis and cell migration. Heparanase expression is often associated with enhanced tumor aggressiveness and chemoresistance. We previously demonstrated that increased heparanase expression in tumor cells enhances secretion and alters the composition of tumor-released exosomes. In the present study, we discovered that extracellular vesicles (EVs) secreted by human multiple myeloma cells growing in hypoxic conditions exhibited elevated levels of heparanase cargo compared to EVs from cells growing in normoxic conditions. When macrophages (RAW 264.7 monocyte/macrophage-like cells) were exposed to EVs released by tumor cells growing in either hypoxic or normoxic conditions, macrophage migration and invasion was elevated by EVs from hypoxic conditions. The elevated invasion of macrophages was blocked by a monoclonal antibody that inhibits heparanase enzyme activity. Moreover, the heparanase-bearing EVs from hypoxic cells greatly enhanced endothelial cell tube formation consistent with the known role of heparanase in promoting angiogenesis. EVs from hypoxic tumor cells when compared with EVs from normoxic cells also enhanced cancer stemness properties of both CAG and RPMI 8226 human myeloma cells. Together these data indicate that under hypoxic conditions, tumor cells secrete EVs having an elevated level of heparanase as cargo. These EVs can act on both tumor and non-tumor cells, enhancing tumor progression and tumor cell stemness that likely supports chemoresistance and relapse of tumor.</p>","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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