Recent Studies of Mitochondrial SLC25: Integration of Experimental and Computational Approaches.
The mitochondrial carrier family (solute carrier family 25) is a super family of nuclearencoded transporters localized on the inner mitochondrial membranes. In human, the mitochondrial carrier family has 53 members, all with a ternary structure of six transmembrane α-helices. The structure of mitochondrial carrier family has three repeats of conservative motifs. The members of this family connect the inter membrane space and matrix of mitochondria, and transport various important small molecules across the inner membrane. In the present review, we have highlighted the limitations of traditional research methods to gain the accurate knowledge of membrane proteins. We have focused on recent emerging computational strategies such as molecular modeling, molecular dynamics, and quantitative structure-activity relationship to predict the structure and function of membrane proteins at atomic resolution in the absence of experimental data. This review aims to summarize a comprehensive introduction of recent discoveries about the biological investigations of the structure and transport mechanism of mitochondrial carriers, which are useful for further investigation on diseases and drug developments related to mitochondrial carrier deficiency, especially the combination of traditional experiments and emerging computational strategies.
Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Yan-Jing
YJ
Wang
Department of Chemistry, Rhodes University, Grahamstown 6139, South Africa.
Faez Iqbal
FI
Khan
Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Qin
Q
Xu
Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Dong-Qing
DQ
Wei
D001692:Biological Transport; D000076722:Drug Development; D030342:Genetic Diseases, Inborn / Q000378:metabolism / Q000628:therapy; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D062105:Molecular Docking Simulation / Q000379:methods*; D009154:Mutation; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D015398:Signal Transduction
D033681:Mitochondrial Membrane Transport Proteins; D004364:Pharmaceutical Preparations
MD simulations; Mitochondrial carrier; SLC25; drug developments; homology modeling; mitochondrial diseases; transport mechanism