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New Insights into Structure and Function of Nuclear Receptors

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The nuclear receptor superfamily is a large group of structurally and functionally related conditional transcription factors. Each family member integrates diverse signal inputs to regulate multiple steps of gene expression and some receptors also influence cytoplasmic and membrane signaling pathways. Many ...

The nuclear receptor superfamily is a large group of structurally and functionally related conditional transcription factors. Each family member integrates diverse signal inputs to regulate multiple steps of gene expression and some receptors also influence cytoplasmic and membrane signaling pathways. Many nuclear receptors respond to small lipophilic molecules which include endocrine hormones and byproducts of intermediary metabolism. Individual receptors may bind more than one ligand type with different consequences for their activities. Receptor activity is also strongly influenced by a range of post-translational modifications, especially orphan receptors which may not bind small molecules. The nuclear receptors function in concert with hundreds of partners which are also subject to influences of diverse signaling inputs and include chaperone complexes which prime receptors for ligand binding and activity and large numbers of effector proteins which mediate receptor outputs.

The nuclear receptors play central roles in normal physiology, development and disease and are among the most important targets for pharmaceuticals. Atomic structures of many individual receptor domains and several full length or multidomain receptor complexes are known. It is now clear, however, that the receptors are dynamic entities with highly context-selective or graded activities that can be differentially influenced by ligand type, partner protein spectrum, modification state and other inputs. Improved understanding of dynamic and context-specific alterations in receptor structure and their influences on function could open new avenues for therapeutic interventions.

This Research Topic will focus on the current state of knowledge of the structural underpinnings of diverse receptor functions. We invite reviews, mini-reviews and other article types that focus on receptor structure and dynamics and the influences of ligands, partners and modification state, with a strong emphasis on new opportunities for therapeutics that could emerge from better understanding of these processes.


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