Effects of phosphorylation on the intrinsic propensity of backbone conformations of serine/threonine

He, Erbin; Gao, Yan; Zhang, Jian; Wang, Jun; Li, Wenfei

doi:10.1007/s10867-015-9405-0

Cited by 9 publications

(8 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Supplementary Figure S2A (in SI) shows the time evolution of Hydrogen bond forms between the Lyase domain and Serine 44 for WT and pS44 whereas Supplementary Figure S2B shows the time evolution of hydrogen form between the D sub-domain and S44 for pS44. It is clear from the figure that the pS44 residue forms more H-bonds compared to the S44 residue in WT, consistent with the literature ( Mandell et al, 2007 ; He et al, 2016 ). Thus, H-bond analysis signifies the role of hydrogen bonds in opening up the structure of the pS44 system.…”

Section: Resultssupporting

confidence: 91%

Phosphorylation Induced Conformational Transitions in DNA Polymerase β

Srivastava

Idriss

Taha

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

DNA polymerase β (pol β) is a member of the X- family of DNA polymerases that catalyze the distributive addition of nucleoside triphosphates during base excision DNA repair. Previous studies showed that the enzyme was phosphorylated in vitro with PKC at two serines (44 and 55), causing loss of DNA polymerase activity but not DNA binding. In this work, we have investigated the phosphorylation-induced conformational changes in DNA polymerase β in the presence of Mg ions. We report a comprehensive atomic resolution study of wild type and phosphorylated DNA polymerase using molecular dynamics (MD) simulations. The results are examined via novel methods of internal dynamics and energetics analysis to reveal the underlying mechanism of conformational transitions observed in DNA pol β. The results show drastic conformational changes in the structure of DNA polymerase β due to S44 phosphorylation. Phosphorylation-induced conformational changes transform the enzyme from a closed to an open structure. The dynamic cross-correlation shows that phosphorylation enhances the correlated motions between the different domains. Centrality network analysis reveals that the S44 phosphorylation causes structural rearrangements and modulates the information pathway between the Lyase domain and base pair binding domain. Further analysis of our simulations reveals that a critical hydrogen bond (between S44 and E335) disruption and the formation of three additional salt bridges are potential drivers of these conformational changes. In addition, we found that two of these additional salt bridges form in the presence of Mg ions on the active sites of the enzyme. These results agree with our previous study of DNA pol β S44 phosphorylation without Mg ions which predicted the deactivation of DNA pol β. However, the phase space of structural transitions induced by S44 phosphorylation is much richer in the presence of Mg ions.

show abstract

Section: Resultssupporting

confidence: 91%

Phosphorylation Induced Conformational Transitions in DNA Polymerase β

Srivastava

Idriss

Taha

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…Sequence analysis of TTBK2 reveals that TTBK2 is highly enriched in serine residues at its C-terminus, which is also the region that associates with CEP164 (Čajánek and Nigg, 2014). Recent studies have shown that the phosphorylation of serine residues increases the intrinsic propensity of local backbone structure to form the polyproline II helix (He et al, 2016). Thus, it is possible that serum starvation induces a conformational change in TTBK2 by phosphorylating/dephosphorylating the enrichment of serine residues at its C-terminus.…”

Section: Lo Et Almentioning

confidence: 99%

Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation

Lin

Yang

et al. 2019

Journal of Cell Biology

View full text Add to dashboard Cite

Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Tau-tubulin kinase-2 (TTBK2) is genetically linked to spinocerebellar ataxia type 11, and its kinase activity is crucial for ciliogenesis. Although it has been shown that TTBK2 is recruited to the centriole by distal appendage protein CEP164, little is known about TTBK2 substrates associated with its role in ciliogenesis. Here, we perform superresolution microscopy and discover that serum starvation results in TTBK2 redistribution from the periphery toward the root of distal appendages. Our biochemical analyses uncover CEP83 as a bona fide TTBK2 substrate with four phosphorylation sites characterized. We also demonstrate that CEP164-dependent TTBK2 recruitment to distal appendages is required for subsequent CEP83 phosphorylation. Specifically, TTBK2-dependent CEP83 phosphorylation is important for early ciliogenesis steps, including ciliary vesicle docking and CP110 removal. In summary, our results reveal a molecular mechanism of kinase regulation in ciliogenesis and identify CEP83 as a key substrate of TTBK2 during cilia initiation.

show abstract

“…Extensive protein modifications, such as ubiquitylation and sumoylation, are not observed for honey bee Vg ( Havukainen et al, 2011 ; Havukainen et al, 2012 ), but the protein is known to be phosphorylated and glycosylated ( Havukainen et al, 2011 ) (extent and exact positions of these PTMs are unknown). There are well-documented examples of phosphorylation and glycosylation providing increased solubility ( Darewicz et al, 1998 ; Darewicz et al, 1999 ; Srikanth et al, 2010 ; Broyard and Gaucheron, 2015 ), resistance to disordered elements against proteases ( Havukainen et al, 2011 ; Havukainen et al, 2012 ; Niu et al, 2015 ), modulation of the conformational propensities of flexible elements ( Fraser et al, 2010 ; Kurotani and Sakurai, 2015 ; He et al, 2016 ), and steric hindrances or complementarity for ligand binding or domain reorganization ( Dean and Koshland, 1990 ; Shipley et al, 1993 ). Methylation or acetylation of Vg could also conceivably be involved.…”

Section: Post-translational Modificationsmentioning

confidence: 99%

How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal

Leipart¹,

Halskau²,

Amdam

2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Vitellogenin (Vg) is a phylogenetically broad glycolipophosphoprotein. A major function of this protein is holding lipid cargo for storage and transportation. Vg has been extensively studied in honey bees (Apis mellifera) due to additional functions in social traits. Using AlphaFold and EM contour mapping, we recently described the protein structure of honey bee Vg. The full-length protein structure reveals a large hydrophobic lipid binding site and a well-defined fold at the C-terminal region. Now, we outline a shielding mechanism that allows the C-terminal region of Vg to cover a large hydrophobic area exposed in the all-atom model. We propose that this C-terminal movement influences lipid molecules’ uptake, transport, and delivery. The mechanism requires elasticity in the Vg lipid core as described for homologous proteins in the large lipid transfer protein (LLTP) superfamily to which Vg belongs. Honey bee Vg has, additionally, several structural arrangements that we interpret as beneficial for the functional flexibility of the C-terminal region. The mechanism proposed here may be relevant for the Vg molecules of many species.

show abstract

Effects of phosphorylation on the intrinsic propensity of backbone conformations of serine/threonine

Cited by 9 publications

References 57 publications

Phosphorylation Induced Conformational Transitions in DNA Polymerase β

Phosphorylation Induced Conformational Transitions in DNA Polymerase β

Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation

How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal

Contact Info

Product

Resources

About