Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function

Abstract

Cytokines are key mediators of cellular communication and regulators of biological advents. The timing, quantity and localization of cytokines are key features in producing specific biological outcomes, and thus have been thoroughly studied and reviewed while continuing to be a focus of the cytokine biology community. Due to the complexity of cellular signaling and multitude of factors that can affect signaling outcomes, systemic level studies of cytokines are ongoing. Despite their small size, cytokines can exhibit structurally promiscuous and dynamic behavior that plays an equally important role in biological activity. In this review using case studies, we highlight the recent insight gained from observing cytokines through a molecular lens and how this may complement a system-level understanding of cytokine biology, explain diversity of downstream signaling events, and inform therapeutic and experimental development.

Statistical and network analyses reveal mechanisms for the enhancement of macrophage immunity by manganese in Mycobacterium tuberculosis infection

“…The family of tumor necrosis factors, interleukins, and chemokines are the main cytokines. Most of the mechanisms that maintain homeostasis in the body depend on cytokine production and response, which are produced by every nucleated cell [ 12 ]. Cytokines can bind to receptors on the surface of the cell membrane and then activate signaling pathways, such as the JAK-STAT signaling pathway and the P53 signaling pathway, and play a crucial role in cell proliferation, differentiation, and immune regulation [ 13 ].…”

Modulation of IL-17 backbone dynamics reduces receptor affinity and reveals a new inhibitory mechanism

“…Previous studies on a number of cytokines have highlighted their dynamic nature, which is believed to play an important role in allowing them a range of diverse binding partners. 55 Indeed, structural studies of the IL-17 dimers have often failed to fully explain important features of the IL-17 receptor complexes, leading to the suggestion that the crystal structures might not be fully representative of the solution state. 12 We have previously reported 21 a phenomenological analysis of solution NMR data for IL-17A, AF and F, which established a link between the varying dynamic nature of the IL-17 dimers and their affinity for IL- .…”