title: Structural studies of GDNF family ligands with their receptors-Insights into ligand recognition and activation of receptor tyrosine kinase RET.
abstract: RET is the receptor for glial cell line-derived neurotrophic factor family of ligands (GFLs). It is different from most other members in the receptor tyrosine kinase (RTK) family with the requirement of a co-receptor, GFRα, for ligand recognition and activation. Through the common signal transducer RET, GFLs are crucial for the development and maintenance of distinct sets of central and peripheral neurons, which has led to a series of studies towards understanding the structure, function and signaling mechanisms of GFLs with GFRα and RET receptors. Here I summarize our current understanding of the molecular basis underlying ligand recognition and activation of RET, focusing on the interactions of GFLs with their respective GFRα receptors, the recently determined crystal structure of RET extracellular region and a proposed GFL-GFRα-RET ternary complex model based on extensive structural, biochemical and functional data. This article is part of a Special Issue entitled: Emerging recognition and activation mechanisms of receptor tyrosine kinases.
authors.affiliation: Center for Structural Biology, School of Life Sciences, Ministry of Education Key Laboratory of Protein Science, Medical Science Building C226, Tsinghua University, Beijing 100084, PR China. Electronic address: xinquanwang@mail.tsinghua.edu.cn.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001665:Binding Sites; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D051096:Proto-Oncogene Proteins c-ret / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051098:Glial Cell Line-Derived Neurotrophic Factors; D008024:Ligands; D051096:Proto-Oncogene Proteins c-ret
keywords: GDNF family ligand; Ligand recognition; Receptor activation; Receptor tyrosine kinase RET