Matrix Biology最新文献

The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis 细胞外基质在炎症性肠病相关肠道纤维化中的功能作用

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-05-19 DOI: 10.1016/j.matbio.2025.05.001

Si-Nan Lin , Jie Wang , Pranab K. Mukherjee , Ido Veisman , William․ J․ Massey , Ren Mao , Jyotsna Chandra , Claudio Fiocchi , Florian Rieder

{"title":"The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis","authors":"Si-Nan Lin , Jie Wang , Pranab K. Mukherjee , Ido Veisman , William․ J․ Massey , Ren Mao , Jyotsna Chandra , Claudio Fiocchi , Florian Rieder","doi":"10.1016/j.matbio.2025.05.001","DOIUrl":"10.1016/j.matbio.2025.05.001","url":null,"abstract":"<div><div>Intestinal fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in the bowel wall. Complications, such as strictures that require surgical intervention in a large proportion of patients, are considered an inevitable consequence of chronic inflammation in inflammatory bowel disease (IBD) and leads to severe complications. The study of intestinal fibrosis in IBD has been traditionally focused on the associated immune process, and the role of the ECM itself has been largely overlooked. More recent studies have now clearly demonstrated that ECM is not simply a passive bystander of inflammation-driven fibrosis but is instead an active participant in the initiation and progression of the fibrogenic process. In this narrative review, we first describe the composition and function of the ECM components under physiological and pathological conditions of the gut. Then, we review the alterations of the intestinal ECM in IBD-associated fibrosis and the impact of fibrotic ECM on intestinal biology and function. We next critically evaluate the existing experimental systems to study the intestinal ECM, both <em>in vitro</em> and <em>in vivo</em>. We conclude by discussing the unique challenges that still exist to better understand the role of the ECM in intestinal fibrosis, and its potential diagnostic and therapeutic implications.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"139 ","pages":"Pages 29-48"},"PeriodicalIF":4.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interactions between cancer-associated fibroblasts and the extracellular matrix in oesophageal cancer 食管癌中癌相关成纤维细胞与细胞外基质的相互作用。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-05-14 DOI: 10.1016/j.matbio.2025.05.003

Subashan Vadibeler , Shannique Clarke , Su M. Phyu , Eileen E. Parkes

{"title":"Interactions between cancer-associated fibroblasts and the extracellular matrix in oesophageal cancer","authors":"Subashan Vadibeler , Shannique Clarke , Su M. Phyu , Eileen E. Parkes","doi":"10.1016/j.matbio.2025.05.003","DOIUrl":"10.1016/j.matbio.2025.05.003","url":null,"abstract":"<div><div>Stromal components of the tumour microenvironment, such as cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM), are actively involved in tumorigenesis. CAFs and the ECM co-evolve with resultant molecular and mechanical pressure on tumour cells mediated by CAFs via the ECM. Meanwhile, ECM fibers determine CAF differentiation and activity, establishing a protumorigenic feed-forward loop. Oesophageal cancer carries a high morbidity and mortality, and curative surgical resection is only an option for a limited number of patients while early lymphatic spread and poor therapeutic responses are common. Although studies report marked heterogeneity in investigation of the stromal density of gastrointestinal cancers, it is generally accepted that oesophageal cancer is highly fibrotic, and stromal components like CAFs may outnumber cancer cells. Therefore, a comprehensive understanding of the reciprocal interaction between CAFs and the ECM in oesophageal cancer is essential to improving diagnostics and prognostication, as well as designing innovative anti-cancer strategies. Here, we summarise current understanding of oesophageal cancer from a stromal perspective. Then, we discuss that CAFs and the ECM in oesophageal cancer can independently and synergistically contribute to tumour progression and therapeutic resistance. We also summarise potential stromal targets that have been described in transcriptomic analyses, highlighting those validated in downstream experimental studies. Importantly, clinical translation of stromal-targeting strategies in oesophageal cancer is still in its infancy but holds significant promise for future therapeutic combinations.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"139 ","pages":"Pages 49-60"},"PeriodicalIF":4.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential modulation of endothelial cell functionality by LRP1 expression in fibroblasts and cancer-associated fibroblasts via paracrine signals and matrix remodeling 通过旁分泌信号和基质重塑，LRP1在成纤维细胞和癌症相关成纤维细胞中的表达对内皮细胞功能的差异调节。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-05-14 DOI: 10.1016/j.matbio.2025.05.004

Julie Martin , Auréana Falaise , Sara Faour , Christine Terryn , Cathy Hachet , Émilie Thiébault , Louise Huber , Pierre Nizet , Damien Rioult , Rodolphe Jaffiol , Stéphanie Salesse , Stéphane Dedieu , Benoit Langlois

{"title":"Differential modulation of endothelial cell functionality by LRP1 expression in fibroblasts and cancer-associated fibroblasts via paracrine signals and matrix remodeling","authors":"Julie Martin , Auréana Falaise , Sara Faour , Christine Terryn , Cathy Hachet , Émilie Thiébault , Louise Huber , Pierre Nizet , Damien Rioult , Rodolphe Jaffiol , Stéphanie Salesse , Stéphane Dedieu , Benoit Langlois","doi":"10.1016/j.matbio.2025.05.004","DOIUrl":"10.1016/j.matbio.2025.05.004","url":null,"abstract":"<div><div>LRP1 is a multifunctional endocytosis receptor involved in the regulation of cancer cell aggressiveness, fibroblast phenotype and angiogenesis. In breast cancer microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and tumor niche composition. LRP1 expression was described in fibroblasts and CAFs but remains poorly understood regarding its impact on endothelial cell behavior and angiocrine signaling. We analyzed the angio-modulatory effect of LRP1 expression in murine embryonic fibroblasts (MEFs) and breast cancer-educated CAF<sub>2</sub> cells. We employed conditioned media and fibroblast-derived matrices to model fibroblastic cells angiogenic effects on human umbilical vein endothelial cells (HUVEC). Neither the extracellular matrix assembled by MEFs knock-out for LRP1 (PEA-13) nor their secretome modify the migration of HUVEC as compared to wild-type. Conversely, LRP1-deficient CAF<sub>2</sub> secretome and matrices stimulate endothelial cell migration. Using spheroids, we demonstrate that PEA-13 secretome does not affect HUVEC angio-invasion. By contrast, CAF<sub>2</sub> secretome invalidated for LRP1 stimulates endothelial sprouting as compared to controls. In addition, it specifically stabilized peripheral VE-cadherin-mediated endothelial cell junctions. A global proteomic analysis revealed that LRP1 expression in CAFs orchestrates a specific mobilization of secreted matricial components, surface receptors and membrane-associated proteins at the endothelial cell surface, thereby illustrating the deep influence exerted by LRP1 in angiogenic signals emitted by activated fibroblasts.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"139 ","pages":"Pages 61-76"},"PeriodicalIF":4.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Load activated FGFR and beta1 integrins target distinct chondrocyte mechano-response genes 负载激活的FGFR和β 1整合素靶向不同的软骨细胞机械反应基因。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-05-14 DOI: 10.1016/j.matbio.2025.05.002

Helen F. Dietmar , Pia A. Weidmann , Paolo Alberton , Terrilyn Teichwart , Matthias Gerstner , Tobias Renkawitz , Andrea Vortkamp , Attila Aszodi , Wiltrud Richter , Solvig Diederichs

{"title":"Load activated FGFR and beta1 integrins target distinct chondrocyte mechano-response genes","authors":"Helen F. Dietmar , Pia A. Weidmann , Paolo Alberton , Terrilyn Teichwart , Matthias Gerstner , Tobias Renkawitz , Andrea Vortkamp , Attila Aszodi , Wiltrud Richter , Solvig Diederichs","doi":"10.1016/j.matbio.2025.05.002","DOIUrl":"10.1016/j.matbio.2025.05.002","url":null,"abstract":"<div><div>In response to mechanical stimuli, chondrocytes adapt their transcriptional activity, thereby shaping the cellular mechano-response; however, it remains unclear whether the activation of cell surface receptors during mechanical loading converge in the activation of the same mechano-response genes, or whether pathway-specific genes can be defined. We aimed to determine whether load-activated FGF/FGFR signalling and β1 integrins activate ERK and control the same or distinct subsets of mechano-regulated genes. To this end, tissue-engineered neocartilage was generated from murine costal chondrocytes or human articular chondrocytes and subjected to dynamic unconfined compression with or without FGFR inhibition. To assess the role of β1 integrins, neocartilage was generated from embryonic β1 integrin-deficient or wild type costal chondrocytes.</div><div>Load-activated FGFR signalling drove ERK activation in murine chondrocytes, and partially also in human chondrocytes, and mechano-response genes could be classified according to their regulation: <em>Fosl1, Itga5, Ngf</em> and <em>Timp1</em> were regulated by load-activated FGFR depending on the developmental stage, whereas β1 integrins controlled <em>Inhba</em> expression. In human chondrocytes, load-activated FGFR signalling controlled expression of <em>BMP2, PTGS2</em> and <em>DUSP5,</em> but not <em>FOSB.</em></div><div>We show here that the chondrocyte loading response is coordinated by concurrent activation of multiple receptors, and identified for the first time distinct target genes of activated receptors. These insights open up the opportunity to pharmacologically shape the mechano-response of chondrocytes in future studies with promising implications for the management of osteoarthritis and the development of novel therapeutic strategies.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"139 ","pages":"Pages 77-89"},"PeriodicalIF":4.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The life cycle of type IV collagen IV型胶原的生命周期

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-04-28 DOI: 10.1016/j.matbio.2025.04.004

Sandhya Srinivasan, David R. Sherwood

{"title":"The life cycle of type IV collagen","authors":"Sandhya Srinivasan, David R. Sherwood","doi":"10.1016/j.matbio.2025.04.004","DOIUrl":"10.1016/j.matbio.2025.04.004","url":null,"abstract":"<div><div>Type IV collagen is a large triple helical molecule that forms a covalently cross-linked network within basement membranes (BMs). Type IV collagen networks play key roles in mechanically supporting tissues, shaping organs, filtering blood, and cell signaling. To ensure tissue health and function, all aspects of the type IV collagen life cycle must be carried out accurately. However, the large triple helical structure and complex life-cycle of type IV collagen, poses many challenges to cells and tissues. Type IV collagen predominantly forms heterotrimers and to ensure proper construction, expression of the distinct α-chains that comprise a heterotrimer needs tight regulation. The α-chains must also be accurately modified by several enzymes, some of which are specific to collagens, to build and stabilize the triple helical trimer. In addition, type IV collagen is exceptionally long (400 nm) and thus the packaging and trafficking of the triple helical trimer from the ER to the Golgi must be modified to accommodate the large type IV collagen molecule. During ER-to-Golgi trafficking, as well as during secretion and transport in the extracellular space, type IV collagen also associates with specific chaperone molecules that maintain the structure and solubility of collagen IV. Type IV collagen trimers are then delivered to BMs from local and distant sources where they are integrated into BMs by interactions with cell surface receptors and many diverse BM resident proteins. Within BMs type IV collagen self-associates into a network and is crosslinked by BM resident enzymes. Finally, homeostatic type IV collagen levels in BMs are maintained by poorly understood mechanisms involving proteolysis and endocytosis. Here, we provide an overview of the life cycle of collagen IV, highlighting unique mechanisms and poorly understood aspects of type IV collagen regulation.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"139 ","pages":"Pages 14-28"},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain vascular basement membrane: Comparison of human and mouse brain at the transcriptomic and proteomic levels 脑血管基底膜：人类和小鼠大脑转录组学和蛋白质组学水平的比较

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-04-26 DOI: 10.1016/j.matbio.2025.04.003

Nan Zhao , Alexander F. Pessell , Tracy D. Chung , Peter C. Searson

{"title":"Brain vascular basement membrane: Comparison of human and mouse brain at the transcriptomic and proteomic levels","authors":"Nan Zhao , Alexander F. Pessell , Tracy D. Chung , Peter C. Searson","doi":"10.1016/j.matbio.2025.04.003","DOIUrl":"10.1016/j.matbio.2025.04.003","url":null,"abstract":"<div><div>The cerebrovascular basement membrane (BM) is a key component of the blood-brain barrier (BBB). The BM provides structural support for brain microvascular endothelial cells and the supporting cells of the neurovascular unit, and facilitates cell signaling through adhesion receptors, regulates the concentration of soluble factors, and serves as an additional barrier for transport. However, our understanding of the composition of BM remains incomplete. Here we analyze recent proteomic and genomic data to assess the composition of BM in human and mouse brain, and in tissue-engineered BBB models. All data sets confirm that the main components of brain BM are collagen IV a1/2 and laminin, along with agrin, perlecan, and nidogen. Transcriptomic data from human BMECs suggests that the main laminin isoform is Laminin 321, while transcriptomic data from mice and proteomic data from mice and humans suggest that Laminin 521 is the predominant isoform. Transcriptomic data from iBMECs suggest that Laminin 511 is the predominant isoform. The supporting molecules agrin, perlecan, and nidogen were detected at significant levels in all studies, although only nidogen 1 was detected in the human transcriptomic data sets. No significant differences in human BM composition were observed in BMECs along the arterio-venous axis, or in comparison of healthy and AD brains.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"139 ","pages":"Pages 1-13"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ECM, integrins, and DDRs: A nexus of cancer progression, therapy, and future directions ECM、整合素和ddr：癌症进展、治疗和未来方向的关系

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-04-12 DOI: 10.1016/j.matbio.2025.04.002

Md Al Azim, Julie S Di Martino

引用次数: 0

Oligomerisation of pentraxin-3: Insights from cryoEM 五胜肽-3的寡聚化：低温电子显微镜的启示。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-04-03 DOI: 10.1016/j.matbio.2025.04.001

Antonio Inforzato , Anthony J. Day

{"title":"Oligomerisation of pentraxin-3: Insights from cryoEM","authors":"Antonio Inforzato , Anthony J. Day","doi":"10.1016/j.matbio.2025.04.001","DOIUrl":"10.1016/j.matbio.2025.04.001","url":null,"abstract":"<div><div>Pentraxin-3 (PTX3) is a secreted protein with roles in the stabilisation of hyaluronan-rich extracellular matrices involved in reproductive biology and inflammatory processes, as well as additional functions in innate immunity and cancer. Our recent structural studies (Shah <em>et al.</em>, 2025; DOI:10.1016/j.matbio.2025.01.002), involving X-ray crystallography, cryo-electron microscopy (cryoEM) and AlphaFold modelling, have provided clues as to how PTX3 becomes assembled into an octamer from eight identical protomer subunits. Here it was proposed that four protomers initially form a tetramer, composed of a highly extended N-terminal region consisting of coiled-coil structures and C-terminal pentraxin domains, where two tetramers then immediately align and associate via an extensive network of salt bridges, allowing stabilisation of the octamer via the formation of disulphide bonds. However, a paper published around the same time provides an alternative perspective (Guo <em>et al</em>., 2025; DOI: 10.1016/j.ijbiomac.2024.139207). The authors propose, based on cryoEM analyses, that in addition to octamers, stable dimers, tetramers and hexamers of PTX3 can also assemble, where it is the dimers that provide the ‘building blocks’ for generation of the various oligomeric forms. In this commentary we suggest that the presence of dimers, tetramers and hexamers is likely an artefact of the construct used in recombinant expression, since the existence of these oligomers is not consistent with other studies on PTX3. We also provide a model to clarify how protomers become assembled into an octamer via sequential formation of a disulphide-linked tetramer, non-covalent association of two tetramers through aligned ionic interactions and the formation of disulphide bonds between the C-terminal pentraxin domains.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"138 ","pages":"Pages 22-26"},"PeriodicalIF":4.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toward a rational therapeutic for elastin related disease: Key considerations for elastin based regenerative medicine strategies 迈向弹性蛋白相关疾病的合理治疗：基于弹性蛋白的再生医学策略的关键考虑。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-03-28 DOI: 10.1016/j.matbio.2025.03.003

Meysam Ganjibakhsh , Yanina Tkachenko , Russell H. Knutsen , Beth A. Kozel

{"title":"Toward a rational therapeutic for elastin related disease: Key considerations for elastin based regenerative medicine strategies","authors":"Meysam Ganjibakhsh , Yanina Tkachenko , Russell H. Knutsen , Beth A. Kozel","doi":"10.1016/j.matbio.2025.03.003","DOIUrl":"10.1016/j.matbio.2025.03.003","url":null,"abstract":"<div><div>Elastin is a connective tissue protein, produced from the <em>ELN</em> gene, that provides elasticity and recoil to tissues that stretch, such as the large arteries of the body, lung parenchyma, skin, ligaments and elastic cartilages. It is produced as a soluble monomer, tropoelastin, that when cross-linked in the extracellular space generates a polymer that is extraordinarily stable, with a predicted half-life of >70 years. Although data suggest ongoing elastin transcription, it is rare to see new elastin deposited outside of its tight developmental window. Consequently, elastin-related disease comes about primarily in one of three scenarios: (1) inadequate elastin deposition, (2) production of poor-quality elastic fibers, or (3) increased destruction of previously deposited elastin. By understanding the pathways controlling elastin production and maintenance, we can design new therapeutics to thwart those abnormal processes. In this review, we will summarize the diseases arising from genetic and environmental alteration of elastin (Williams syndrome, supravalvar aortic stenosis, autosomal dominant cutis laxa, and ELN-related vascular and connective tissue dysfunction) and then describe the mechanisms controlling elastin production and maintenance that might be manipulated to generate novel therapeutics aimed at these conditions. We will end by summarizing existing therapeutic strategies targeting these disease mechanisms before outlining future approaches that may better solve the challenges associated with elastin based regenerative medicine.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"138 ","pages":"Pages 8-21"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights on perlecan and Schwartz–Jampel syndrome 关于perlecan和Schwartz-Jampel综合征的结构见解。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-03-19 DOI: 10.1016/j.matbio.2025.03.002

Anil A. Sohail , M. Kristian Koski , Lloyd W. Ruddock

{"title":"Structural insights on perlecan and Schwartz–Jampel syndrome","authors":"Anil A. Sohail , M. Kristian Koski , Lloyd W. Ruddock","doi":"10.1016/j.matbio.2025.03.002","DOIUrl":"10.1016/j.matbio.2025.03.002","url":null,"abstract":"<div><div>Perlecan is an essential multi-domain, disulfide bond rich basement membrane protein. Mutations in perlecan cause Schwartz-Jampel syndrome and dyssegmental dysplasia. While there has been a large body of experimental work reported on perlecan, there is only minimal structural information available to date. There is no prior structural data for region 3 of perlecan in which some Schwartz-Jampel syndrome causing point mutations have been reported. Here, we produce constructs of the disulfide rich region 3 of perlecan along with five mutations previously reported to cause Schwatz-Jampel syndrome. Four of the mutations resulted in decreased yields and thermal stability compared to the wild-type protein. In contrast, the P1019L mutation was produced in good yields and showed higher thermal stability than the wild-type protein. The crystal structures for both the wild-type and P1019L mutation were solved. As expected, both showed laminin IV-like and laminin-type EGF-like domains, with the P1019L mutation resulting in only a minor conformational change in a loop region and no significant changes in regular secondary or tertiary structure.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"138 ","pages":"Pages 1-7"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0