Adverse effects of Alport syndrome-related Gly missense mutations on collagen type IV: Insights from molecular simulations and experiments
文献类型: 外文期刊
第一作者: Yeo, Jingjie
作者: Yeo, Jingjie;Qiu, Yimin;Kaplan, David L.;Yeo, Jingjie;Jung, Gang Seob;Buehler, Markus J.;Yeo, Jingjie;Zhang, Yong-Wei;Yeo, Jingjie;Qiu, Yimin
作者机构:
关键词: Alport syndrome; Collagen type IV; Molecular dynamics simulation; Experimental assays; Integrin binding; Enzyme digestion; Structural stability
期刊名称:BIOMATERIALS ( 影响因子:12.479; 五年影响因子:12.104 )
ISSN: 0142-9612
年卷期: 2020 年 240 卷
页码:
收录情况: SCI
摘要: Patients with Alport syndrome (AS) exhibit blood and elevated protein levels in their urine, inflamed kidneys, and many other abnormalities. AS is attributed to mutations in type IV collagen genes, particularly glycine missense mutations in the collagenous domain of COL4A5 that disrupt common structural motifs in collagen from the repeat (Gly-Xaa-Yaa)(n )amino acid sequence. To characterize and elucidate the molecular mechanisms underlying how AS-related mutations perturb the structure and function of type IV collagen, experimental studies and molecular simulations were integrated to investigate the structure, stability, protease sensitivity, and integrin binding affinity of collagen-like proteins containing amino acid sequences from the alpha 5(IV) chain and AS-related Gly missense mutations. We show adverse effects where (i) three AS-related Gly missense mutations significantly reduced the structural stability of the collagen in terms of decreased melting temperatures and calorimetric enthalpies, in conjunction with a collective drop in the external work needed to unfold the peptides containing mutation sequences; (ii) due to local unwinding around the sites of mutations, these triple helical peptides were also degraded more rapidly by trypsin and chymotrypsin, as these enzymes could access the collagenous triple helix more easily and increase the number of contacts; (iii) the mutations further abolished the ability of the recombinant collagens to bind to integrins and greatly reduced the binding affinities between collagen and integrins, thus preventing cells from adhering to these mutants. Our unified experimental and computational approach provided underlying insights needed to guide potential therapies for AS that ameliorate the adverse effects from AS disease onset and progression.
分类号:
- 相关文献
作者其他论文 更多>>
-
Microscopic insight into the interactions between pea protein and fatty acids during high-moisture extrusion processing
作者:Chen, Qiongling;Zhang, Jinchuang;Zhang, Yujie;Liu, Haodong;Li, Tongqing;Wang, Qiang;Kaplan, David L.
关键词:Pea protein; Fatty acids; Interactions; High-moisture extrusion; Structural changes
-
Application of transglutaminase modifications for improving protein fibrous structures from different sources by high-moisture extruding
作者:Zhang, Jinchuang;Li, Tongqing;Chen, Qiongling;Liu, Haodong;Wang, Qiang;Kaplan, David L.
关键词:Plant proteins; Transglutaminase; High-moisture extrusion; System response parameters; Structural modification; Texturization
-
Improving the Activity of Tryptophan Synthetase via a Nucleic Acid Scaffold
作者:Wang, Yaping;Wang, Xiangyi;Niu, Shuhui;Cheng, Wei;Liu, Xiaoyan;Min, Yong;Qiu, Yimin;Rao, Ben;Zhu, Lei;Wang, Yaping;Wang, Xiangyi;Niu, Shuhui;Cheng, Wei;Ma, Lixin
关键词:tryptophan synthetase; dCE; TrapA; TrapB; nucleic acid scaffold
-
Acaricidal Activity and Field Efficacy Analysis of the Potential Biocontrol Agent Bacillus vallismortis NBIF-001 against Spider Mites
作者:Zhu, Lei;Chen, Ling;Min, Yong;Liu, Fang;Liao, Xianqing;Rao, Ben;Qiu, Yimin;Chen, Wei;Wang, Kaimei;Yang, Ziwen;Zhou, Ronghua;Gong, Yan;Liu, Xiaoyan;Zhu, Lei;Chen, Ling;Min, Yong;Liu, Fang;Liao, Xianqing;Rao, Ben;Qiu, Yimin;Chen, Wei;Wang, Kaimei;Yang, Ziwen;Zhou, Ronghua;Gong, Yan;Liu, Xiaoyan;Zhu, Lei;Chen, Ling;Min, Yong;Liu, Fang;Liao, Xianqing;Rao, Ben;Qiu, Yimin;Chen, Wei;Wang, Kaimei;Yang, Ziwen;Zhou, Ronghua;Gong, Yan;Liu, Xiaoyan;Zhou, Ronghua
关键词:spider mites; Bacillus vallismortis; acaricidal activity; field efficacy; protein BVP8; biocontrol
-
Complete Genome Sequence of Brachybacterium sp. Strain NBEC-018, Isolated from Nematode-Infected Potatoes
作者:Chen, Ling;Wang, Yueying;Liu, Nanxi;Zhu, Lei;Min, Yong;Qiu, Yimin;Tian, Yuxi;Liu, Xiaoyan
关键词:
-
Protein-amylose/amylopectin molecular interactions during high-moisture extruded texturization toward plant-based meat substitutes applications
作者:Chen, Qiongling;Zhang, Jinchuang;Zhang, Yujie;Wang, Qiang;Kaplan, David L.
关键词:Pea protein; Amylose; Amylopectin; Molecular interactions; High-moisture extrusion; Meat substitute
-
High-moisture extruded protein fiber formation toward plant-based meat substitutes applications: Science, technology, and prospect
作者:Zhang, Jinchuang;Chen, Qiongling;Wang, Qiang;Kaplan, David L.
关键词:Plant -based meat substitutes; High -moisture extrusion; Protein sources; Theoretical basis; Process and equipment; Quality evaluation