02486nas a2200277   4500008004100000022001400041245017700055210006900232260000900301300001400310490000700324520149400331653001201825653001301837653001801850653002201868653003301890653002501923100001901948700002001967700002301987700001502010700002602025700002502051856013202076       2024                        eng d  a0739-110200aDe novo structure prediction of meteorin and meteorin-like protein for identification of domains, functional receptor binding regions, and their high-risk missense variants0 aDe novo structure prediction of meteorin and meteorinlike protei  cJUN   a4522-45360 v423 a<p>
	Meteorin (Metrn) and Meteorin-like (Metrnl) are homologous secreted proteins involved in neural development and metabolic regulation. In this study, we have performed de novo structure prediction and analysis of both Metrn and Metrnl using Alphafold2 (AF2) and RoseTTAfold (RF). Based on the domain and structural homology analysis of the predicted structures, we have identified that these proteins are composed of two functional domains, a CUB domain and an NTR domain, connected by a hinge/loop region. We have identified the receptor binding regions of Metrn and Metrnl using the machine-learning tools ScanNet and Masif. These were further validated by docking Metrnl with its reported KIT receptor, thus establishing the role of each domain in the receptor interaction. Also, we have studied the effect of non-synonymous SNPs on the structure and function of these proteins using an array of bioinformatics tools and selected 16 missense variants in Metrn and 10 in Metrnl that can affect the protein stability. This is the first study to comprehensively characterize the functional domains of Metrn and Metrnl at their structural level and identify the functional domains, and protein binding regions. This study also highlights the interaction mechanism of the KIT receptor and Metrnl. The predicted deleterious SNPs will allow further understanding of the role of these variants in modulating the plasma levels of these proteins in disease conditions such as diabetes.</p>
10adomains10aMeteorin10ameteorin-like10amissense variants10aprotein-protein interactions10astructure prediction1 aShankar, Shiva1 aBanarjee, Reema1 aJathar, Swaraj, M.1 aRajesh, S.1 aRamasamy, Sureshkumar1 aKulkarni, Mahesh, J.  uhttps://library.ncl.res.in/content/de-novo-structure-prediction-meteorin-and-meteorin-protein-identification-domains-functional