The Role of Allostery in the Termination of Second Messenger Signaling

Nussinov, Ruth; Tsai, Chung‐Jung

doi:10.1016/j.bpj.2015.07.007

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…As has been shown before for other protein complexes, allostery occurs even in the absence of measurable conformational change (Cooper and Dryden, 1984;Kornev and Taylor, 2015;Tsai et al, 2008). For instance, many protein kinases as well as G-coupled receptors (GPCR) are allosterically regulated; however, no significant conformational changes have ever been detected (Kornev and Taylor, 2015;Nussinov and Tsai, 2015). To provide an atomic-level description and an improved understanding of the allosteric activation and structural communication in the Csm complex, further studies that include molecular simulations and biochemical analysis are required.…”

Section: Model For Type Iii-a Interferencementioning

confidence: 99%

Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference

You

Wang

et al. 2019

Cell

124

243

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Graphical Abstract Highlights d Crystal structure of the type III-A CRISPR-RNA-guided surveillance complex d Cryo-EM structures of cognate and non-cognate target RNA-bound Csm complexes d Complementary and non-complementary 3 0 anti-tag binds at two distinct sites d Target RNA binding allosterically activates ssDNA cleavage and cOA synthesis SUMMARYCsm, a type III-A CRISPR-Cas interference complex, is a CRISPR RNA (crRNA)-guided RNase that also possesses target RNA-dependent DNase and cyclic oligoadenylate (cOA) synthetase activities. However, the structural features allowing target RNAbinding-dependent activation of DNA cleavage and cOA generation remain unknown. Here, we report the structure of Csm in complex with crRNA together with structures of cognate or non-cognate target RNA bound Csm complexes. We show that depending on complementarity with the 5 0 tag of crRNA, the 3 0 anti-tag region of target RNA binds at two distinct sites of the Csm complex. Importantly, the interaction between the non-complementary anti-tag region of cognate target RNA and Csm1 induces a conformational change at the Csm1 subunit that allosterically activates DNA cleavage and cOA generation. Together, our structural studies provide crucial insights into the mechanistic processes required for crRNA-meditated sequencespecific RNA cleavage, RNA target-dependent non-specific DNA cleavage, and cOA generation.GiG-C322 grids (2 mm holes and spacing)

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Section: Model For Type Iii-a Interferencementioning

confidence: 99%

Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference

You

Wang

et al. 2019

Cell

124

243

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“…Allostery is a common biological phenomenon whereby perturbations at a specific site (the allosteric site) cause a conformational change or dynamics at a distal site in the same protein. − Allostery is encoded in single molecules, such as nucleic acids and proteins. − It plays important roles in essential biological processes including cellular signaling, − antigen binding and antibody activation, the ubiquitin–proteasome system, and post-translational modifications . Genetic mutations that alter allosteric communications could cause severe disease as the majority of the disease-causing mutations are located outside of the active sites .…”

Section: Introductionmentioning

confidence: 99%

Engineering an Allosteric Control of Protein Function

2021

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Allosteric regulation in proteins is fundamental to many important biological processes. Allostery has been employed to control protein functions by regulating protein activity. Engineered allosteric regulation allows controlling protein activity in subsecond time scale and has a broad range of applications, from dissecting spatiotemporal dynamics in biochemical cascades to applications in biotechnology and medicine. Here, we review the concept of allostery in proteins and various approaches to identify allosteric sites and pathways. We then provide an overview of strategies and tools used in allosteric protein regulation and their utility in biological applications. We highlight various classes of proteins, where regulation is achieved through allostery. Finally, we analyze the current problems, critical challenges, and future prospective in achieving allosteric regulation in proteins.

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“…The sequencing of individuals has permitted comparisons of corresponding sequences in diseased and healthy tissues, and with the help of computational biology, technological advances have accomplished the imaging and tracking of molecules in action in single cells [21,22,23]. Network science has prospered and become widely used [24] in applications ranging from signaling networks in the cell to those regarding protein molecules in allosteric communications [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44]. Compelling advances have also been made in modeling protein and RNA structures and in mapping chromatin and its dynamics at high resolution [45,46,47,48,49,50,51,52].…”

Section: Introductionmentioning

confidence: 99%

Computational Structural Biology: Successes, Future Directions, and Challenges

et al. 2019

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Computational biology has made powerful advances. Among these, trends in human health have been uncovered through heterogeneous ‘big data’ integration, and disease-associated genes were identified and classified. Along a different front, the dynamic organization of chromatin is being elucidated to gain insight into the fundamental question of genome regulation. Powerful conformational sampling methods have also been developed to yield a detailed molecular view of cellular processes. when combining these methods with the advancements in the modeling of supramolecular assemblies, including those at the membrane, we are finally able to get a glimpse into how cells’ actions are regulated. Perhaps most intriguingly, a major thrust is on to decipher the mystery of how the brain is coded. Here, we aim to provide a broad, yet concise, sketch of modern aspects of computational biology, with a special focus on computational structural biology. We attempt to forecast the areas that computational structural biology will embrace in the future and the challenges that it may face. We skirt details, highlight successes, note failures, and map directions.

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The Role of Allostery in the Termination of Second Messenger Signaling

Cited by 4 publications

References 9 publications

Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference

Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference

Engineering an Allosteric Control of Protein Function

Computational Structural Biology: Successes, Future Directions, and Challenges

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