protein unfolding


Summary: Conformational transitions of the shape of a protein to various unfolded states.

Top Publications

  1. Leinartaité L, Svenningsson P. Folding Underlies Bidirectional Role of GPR37/Pael-R in Parkinson Disease. Trends Pharmacol Sci. 2017;38:749-760 pubmed publisher
    ..Here we review the multiple roles of GPR37 with relevance to potential disease modification and symptomatic therapies of PD and highlight unsolved issues in this field. ..
  2. Silva B, Breydo L, Uversky V. Targeting the chameleon: a focused look at ?-synuclein and its roles in neurodegeneration. Mol Neurobiol. 2013;47:446-59 pubmed publisher
  3. Worden E, Dong K, Martin A. An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome. Mol Cell. 2017;67:799-811.e8 pubmed publisher
    ..The AAA+ motor-driven acceleration of Rpn11 is therefore important to ensure that poly-ubiquitin chains are removed only from committed substrates and fast enough to prevent their co-degradation. ..
  4. Shah R, Chou T, Maize K, Strom A, Finzel B, Wagner C. Inhibition by divalent metal ions of human histidine triad nucleotide binding protein1 (hHint1), a regulator of opioid analgesia and neuropathic pain. Biochem Biophys Res Commun. 2017;491:760-766 pubmed publisher
    ..Thus, hHint1 appears to be structurally sensitive to irreversible inactivation by copper, which may be of neurotoxicological and pharmacological significance. ..
  5. Akbal Delibas B, Jagodzinski F, Haspel N. A conservation and rigidity based method for detecting critical protein residues. BMC Struct Biol. 2013;13 Suppl 1:S6 pubmed publisher
    ..Once the combined methods are integrated into one scoring function, it can be applied to other domains such as estimating functional interfaces. ..
  6. Uversky V, Dave V, Iakoucheva L, Malaney P, Metallo S, Pathak R, et al. Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases. Chem Rev. 2014;114:6844-79 pubmed publisher
  7. Ye Q, Kim D, Dereli I, Rosenberg S, Hagemann G, Herzog F, et al. The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding. EMBO J. 2017;36:2419-2434 pubmed publisher
    ..Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain-closure motif complexes by TRIP13. ..
  8. Owen M, Csizmadia I, Viskolcz B, Strodel B. Protein Stability and Unfolding Following Glycine Radical Formation. Molecules. 2017;22: pubmed publisher
    ..These results provide new evidence on the destabilizing effects of protein oxidation by reactive oxygen species. ..
  9. Manteca A, Alonso Caballero A, Fertin M, Poly S, De Sancho D, Perez Jimenez R. The influence of disulfide bonds on the mechanical stability of proteins is context dependent. J Biol Chem. 2017;292:13374-13380 pubmed publisher

More Information


  1. Chaffey P, Guan X, Chen C, Ruan Y, Wang X, Tran A, et al. Structural Insight into the Stabilizing Effect of O-Glycosylation. Biochemistry. 2017;56:2897-2906 pubmed publisher
    ..This type of knowledge provides a powerful and potentially general mechanism for improving the stability of proteins through glycoengineering...
  2. Singh M, Shivakumaraswamy S, Gummadi S, Manoj N. Role of an N-terminal extension in stability and catalytic activity of a hyperthermostable ?/? hydrolase fold esterase. Protein Eng Des Sel. 2017;30:559-570 pubmed publisher
    ..The results suggest that the N-terminal extension was evolutionarily selected to preserve the stability of the enzyme...
  3. Elmer Dixon M, Bowler B. Site A-Mediated Partial Unfolding of Cytochrome c on Cardiolipin Vesicles Is Species-Dependent and Does Not Require Lys72. Biochemistry. 2017;56:4830-4839 pubmed publisher
    ..For both human and yeast cytochrome c, the K72A mutation has only minor effects on binding to site A, suggesting that other nearby lysines can compensate for the lack of Lys72...
  4. Ewing T, Nguyen Q, Allan R, Gygli G, Romero E, Binda C, et al. Two tyrosine residues, Tyr-108 and Tyr-503, are responsible for the deprotonation of phenolic substrates in vanillyl-alcohol oxidase. J Biol Chem. 2017;292:14668-14679 pubmed publisher
    ..These results indicate that Tyr-108 and Tyr-503 are responsible for the activation of substrates in VAO, providing new insights into the catalytic mechanism of VAO and related enzymes that oxidize para-substituted phenols. ..
  5. Lek M, Cruz S, Ibe N, Beck W, Bielicki J, Weers P, et al. Swapping the N- and C-terminal domains of human apolipoprotein E3 and AI reveals insights into their structure/activity relationship. PLoS ONE. 2017;12:e0178346 pubmed publisher
    ..Together, these results indicate that the functional attributes of apoAI and apoE3 can be conferred on each other and that NT-CT domain interactions significantly modulate their structure and function. ..
  6. Olivera Perez H, Lam L, Dang J, Jiang W, Rodríguez F, Rigali E, et al. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment. FASEB J. 2017;31:4359-4369 pubmed publisher
    ..Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment. ..
  7. Petrosino M, Lori L, Pasquo A, Lori C, Consalvi V, Minicozzi V, et al. Single-Nucleotide Polymorphism of PPAR?, a Protein at the Crossroads of Physiological and Pathological Processes. Int J Mol Sci. 2017;18: pubmed publisher
    ..The nsSNPs PPAR? variants show alteration of dynamics and tertiary contacts that impair the correct reciprocal positioning of helices 3 and 12, crucially important for PPAR? functioning. ..
  8. Datta D, J Swamy M. Fluorescence and circular dichroism studies on the accessibility of tryptophan residues and unfolding of a jacalin-related ?-d-galactose-specific lectin from mulberry (Morus indica). J Photochem Photobiol B. 2017;170:108-117 pubmed publisher
    ..Additionally, pH dependent studies showed that the secondary structure of MLGL is unaltered in the pH range 6.2 to 8.5, but a decrease in lectin activity is observed (~50%) at pH6.2. ..
  9. Dautant A, Meyer P, Georgescauld F. Hydrogen/Deuterium Exchange Mass Spectrometry Reveals Mechanistic Details of Activation of Nucleoside Diphosphate Kinases by Oligomerization. Biochemistry. 2017;56:2886-2896 pubmed publisher
    ..Further HDX-MS studies are necessary to establish the general activation mechanism for other homo-oligomers. ..
  10. Sen S, Goluguri R, Udgaonkar J. A Dry Transition State More Compact Than the Native State Is Stabilized by Non-Native Interactions during the Unfolding of a Small Protein. Biochemistry. 2017;56:3699-3703 pubmed publisher
    ..It was determined that mutation could be used to tune the degree of compaction in the TS...
  11. Mallik S, Ray T, Kundu S. Transiently disordered tails accelerate folding of globular proteins. FEBS Lett. 2017;591:2180-2191 pubmed publisher
    ..These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing. ..
  12. Díaz Casas A, Chazin W, Pastrana Rios B. Prp40 Homolog A Is a Novel Centrin Target. Biophys J. 2017;112:2529-2539 pubmed publisher
    ..These complementary techniques showed for the first time, to our knowledge, that HsPrp40Ap interacts with centrin in vitro, supporting a coupled functional role for these proteins in pre-mRNA splicing. ..
  13. Nold S, Lei H, Mou T, Bowler B. Effect of a K72A Mutation on the Structure, Stability, Dynamics, and Peroxidase Activity of Human Cytochrome c. Biochemistry. 2017;56:3358-3368 pubmed publisher
  14. Stevens C, Rayani K, Singh G, Lotfalisalmasi B, Tieleman D, Tibbits G. Changes in the dynamics of the cardiac troponin C molecule explain the effects of Ca2+-sensitizing mutations. J Biol Chem. 2017;292:11915-11926 pubmed publisher
    ..Our data further suggest that modulation of the structural dynamics is the underlying molecular mechanism for many disease mutations that are far from the regulatory Ca2+-binding site of cTnC. ..
  15. Hyde E, Callow P, Rajasekar K, Timmins P, Patel T, Siligardi G, et al. Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA. Biochem J. 2017;474:3121-3135 pubmed publisher
    ..We propose that the positive co-operativity between KorB, KorA and DNA results from conformational restriction of KorB on binding each partner, while maintaining disorder. ..
  16. Boucher R. Idiopathic pulmonary fibrosis--a sticky business. N Engl J Med. 2011;364:1560-1 pubmed publisher
  17. Sun X, Dyson H, Wright P. Fluorotryptophan Incorporation Modulates the Structure and Stability of Transthyretin in a Site-Specific Manner. Biochemistry. 2017;56:5570-5581 pubmed publisher
    ..The differences in behavior that arise from the replacement of a fluorine at the 5-position of a tryptophan with one at the adjacent 6-position emphasize the delicate balance of stability in the TTR tetramer. ..
  18. Mahalakshmi R, Maurya S, Burdak B, Surti P, Patel M, Jain V. Structural plasticity of T4 transcription co-activator gp33 revealed by a protease-resistant unfolded state. Biochem Biophys Res Commun. 2017;492:61-66 pubmed publisher
    ..Our studies shed new light on the unique structural malleability of gp33 that might be important in its transition from a repressor to a late transcription co-activator. ..
  19. Sluchanko N, Slonimskiy Y, Moldenhauer M, Friedrich T, Maksimov E. Deletion of the short N-terminal extension in OCP reveals the main site for FRP binding. FEBS Lett. 2017;591:1667-1676 pubmed publisher
    ..Here, we demonstrate that the NTE shares specific structural and functional similarities with FRP and discover the main site of OCP-FRP interactions in the OCP-CTD. ..
  20. Kaspersen J, Søndergaard A, Madsen D, Otzen D, Pedersen J. Refolding of SDS-Unfolded Proteins by Nonionic Surfactants. Biophys J. 2017;112:1609-1620 pubmed publisher
    ..We conclude that NIS competes with globular proteins for association with SDS, making it possible to release and refold SDS-denatured proteins by adding sufficient amounts of NIS, unless the protein also interacts with NIS alone. ..
  21. Ouedraogo D, Souffrant M, Vasquez S, Hamelberg D, Gadda G. Importance of Loop L1 Dynamics for Substrate Capture and Catalysis in Pseudomonas aeruginosa d-Arginine Dehydrogenase. Biochemistry. 2017;56:2477-2487 pubmed publisher
    ..Taken together, the computational and experimental data are consistent with the dynamics of loop L1 being important for substrate capture and catalysis in PaDADH. ..
  22. Zanetti Polzi L, Davis C, Gruebele M, Dyer R, Amadei A, Daidone I. Parallel folding pathways of Fip35 WW domain explained by infrared spectra and their computer simulation. FEBS Lett. 2017;591:3265-3275 pubmed publisher
    ..In particular, we propose a hypothesis for why folding via one of these intermediates was not experimentally observed by IR T-jump. ..
  23. Glover K, Li Y, Mukhopadhyay S, Leuthner Z, Chakravarthy S, Colbert C, et al. Structural transitions in conserved, ordered Beclin 1 domains essential to regulating autophagy. J Biol Chem. 2017;292:16235-16248 pubmed publisher
    ..e. the CCD or the BARAD). Our findings have important implications for the relative stability of autophagy-inactive and autophagy-active BECN1 complexes. ..
  24. Rath E, Duff A, Gilbert E, Doherty G, Knott R, Church W. Neutron scattering shows a droplet of oleic acid at the center of the BAMLET complex. Proteins. 2017;85:1371-1378 pubmed publisher
    ..Proteins 2017; 85:1371-1378. © 2017 Wiley Periodicals, Inc. ..
  25. Gómez Ramos L, Degtyareva N, Kovacs N, Holguin S, Jiang L, Petrov A, et al. Eukaryotic Ribosomal Expansion Segments as Antimicrobial Targets. Biochemistry. 2017;56:5288-5299 pubmed publisher
    ..albicans but not in HEK293T cells. The results are consistent with the hypothesis that ESs represent useful targets for chemotherapeutics directed against eukaryotic pathogens...
  26. Voth W, Jakob U. Stress-Activated Chaperones: A First Line of Defense. Trends Biochem Sci. 2017;42:899-913 pubmed publisher
    ..Especially problematic are oxidative, acid, and severe heat stress which induce very rapid and widespread protein unfolding and generate conditions that make canonical chaperones and/or transcriptional responses inadequate to ..
  27. Lenders M, Reimann S, Smits S, Schmitt L. Molecular insights into type I secretion systems. Biol Chem. 2013;394:1371-84 pubmed publisher
    ..This review will provide a detailed view of the components of the translocator and will summarize structural as well as functional data. ..
  28. Armiento A, Moireau P, Martin D, Lepejová N, Doumic M, Rezaei H. The mechanism of monomer transfer between two structurally distinct PrP oligomers. PLoS ONE. 2017;12:e0180538 pubmed publisher
    ..The two groups interact by exchanging monomers through a disintegration process that increases the size of Oa. Our observations suggest that PrP oligomers constitute a highly dynamic population. ..
  29. Rajasekaran N, Naganathan A. A self-consistent structural perturbation approach for determining the magnitude and extent of allosteric coupling in proteins. Biochem J. 2017;474:2379-2388 pubmed publisher
  30. White J, Toptygin D, Cohen R, Murphy N, Hilser V. Structural Stability of the Coiled-Coil Domain of Tumor Susceptibility Gene (TSG)-101. Biochemistry. 2017;56:4646-4655 pubmed publisher
    ..These results support a model whereby the tetramer-monomer equilibrium of TSG101 serves as the cellular reservoir of TSG101, which is effectively outcompeted when its binding partners are present and the heteroternary complex can form...
  31. Cohen R, Pielak G. Quinary interactions with an unfolded state ensemble. Protein Sci. 2017;26:1698-1703 pubmed publisher
    ..Here we show that the cellular environment can also remodel the unfolded state ensemble. ..
  32. Roychoudhury A, Bieker A, Haussinger D, Oesterhelt F. Membrane protein stability depends on the concentration of compatible solutes--a single molecule force spectroscopic study. Biol Chem. 2013;394:1465-74 pubmed publisher
    ..Interestingly, it was revealed that these molecules have different stabilizing effects on protein unfolding at different concentrations...
  33. Igel Egalon A, Moudjou M, Martin D, Busley A, Knäpple T, Herzog L, et al. Reversible unfolding of infectious prion assemblies reveals the existence of an oligomeric elementary brick. PLoS Pathog. 2017;13:e1006557 pubmed publisher
    ..The existence of such an elementary brick scales down the SSD support to a small oligomer and provide a basis of reflexion for prion templating process and propagation...
  34. Nawata M, Tsutsumi H, Kobayashi Y, Unzai S, Mine S, Nakamura T, et al. Heat-induced native dimerization prevents amyloid formation by variable domain from immunoglobulin light-chain REI. FEBS J. 2017;284:3114-3127 pubmed publisher
    ..Structural data are available in the Protein Data Bank under the accession numbers 5XP1 and 5XQY. ..
  35. Kiran U, Regur P, Kreutz M, Sharma Y, Chakraborty A. Intermotif Communication Induces Hierarchical Ca2+ Filling of Caldendrin. Biochemistry. 2017;56:2467-2476 pubmed publisher
    ..EF3 controls initial Ca2+ binding and dictates structural destabilization of EF4. It is likely that this unexpected intermotif communication will have an impact on Ca2+-dependent target interactions. ..
  36. Meric G, Robinson A, Roberts C. Driving Forces for Nonnative Protein Aggregation and Approaches to Predict Aggregation-Prone Regions. Annu Rev Chem Biomol Eng. 2017;8:139-159 pubmed publisher
    ..Challenges with experimental validation of predicted APRs for proteins are briefly discussed. ..
  37. Jakob U, Kriwacki R, Uversky V. Conditionally and transiently disordered proteins: awakening cryptic disorder to regulate protein function. Chem Rev. 2014;114:6779-805 pubmed publisher
  38. Herr A, Thorman A. Hiding in plain sight: immune evasion by the staphylococcal protein SdrE. Biochem J. 2017;474:1803-1806 pubmed publisher
    ..These structures reveal a fascinating mechanism for immune evasion and provide a potential avenue for the development of novel antimicrobial agents to target SdrE. ..
  39. Blancas Mejia L, Martin E, Williams A, Wall J, Ramirez Alvarado M. Kinetic stability and sequence/structure studies of urine-derived Bence-Jones proteins from multiple myeloma and light chain amyloidosis patients. Biophys Chem. 2017;230:89-98 pubmed publisher
    ..the variable and constant domain) immunoglobulin light chains found a strong kinetic control of the protein unfolding for these proteins...