protein interaction domains and motifs


Summary: Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.

Top Publications

  1. Dicke S, Tatge L, Engen P, Culp M, Masterson L. Isothermal titration calorimetry and vesicle leakage assays highlight the differential behaviors of tau repeat segments upon interaction with anionic lipid membranes. Biochem Biophys Res Commun. 2017;493:1504-1509 pubmed publisher
    ..Taken together, these results distinguish the relative selectivity for anionic membranes by each repeat segment and the degree of membrane disruption that results...
  2. Maeda M, Katada T, Saito K. TANGO1 recruits Sec16 to coordinately organize ER exit sites for efficient secretion. J Cell Biol. 2017;216:1731-1743 pubmed publisher
    ..These data suggest that mammalian ER exit sites are organized by TANGO1 acting as a scaffold, in cooperation with Sec16 for efficient secretion. ..
  3. Kartvelishvili E, Tworowski D, Vernon H, Moor N, Wang J, Wong L, et al. Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in human FARS2. Protein Sci. 2017;26:1505-1516 pubmed publisher
    ..Using steady-state kinetic measurements of phenylalanine activation and tRNAPhe aminoacylation, we gained insight into the structural and kinetic effects of mitochondrial disease-related mutations in FARS2 gene. ..
  4. Wobst H, Delsing L, Brandon N, Moss S. Truncation of the TAR DNA-binding protein 43 is not a prerequisite for cytoplasmic relocalization, and is suppressed by caspase inhibition and by introduction of the A90V sequence variant. PLoS ONE. 2017;12:e0177181 pubmed publisher
  5. De Las Rivas J, Fontanillo C. Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PLoS Comput Biol. 2010;6:e1000807 pubmed publisher
  6. Park A, Kim H, Kim I, Roh S, Shin S, Lee J, et al. Crystal structure of cis-dihydrodiol naphthalene dehydrogenase (NahB) from Pseudomonas sp. MC1: Insights into the early binding process of the substrate. Biochem Biophys Res Commun. 2017;491:403-408 pubmed publisher
    ..Furthermore, we defined the initial steps of substrate recognition and identified the early substrate-binding site in the substrate recognition process through the complex structure with ligands. ..
  7. Foreman H, Armstrong J, Santana A, Krug L, Reich N. The replication and transcription activator of murine gammaherpesvirus 68 cooperatively enhances cytokine-activated, STAT3-mediated gene expression. J Biol Chem. 2017;292:16257-16266 pubmed publisher
    ..Our results demonstrate that MHV68 RTA specifically recognizes and recruits activated pTyr705-STAT3 during the lytic phase of infection. ..
  8. Hernandez Zimbron L, Rivas Arancibia S. Deciphering an interplay of proteins associated with amyloid ? 1-42 peptide and molecular mechanisms of Alzheimer's disease. Rev Neurosci. 2014;25:773-83 pubmed publisher
    ..In this review, we present some examples of such associations and the role played by these interactions, which are generally involved in the pathological progression of Alzheimer's disease. ..
  9. Kuldyushev N, Berkut A, Peigneur S, Tytgat J, Grishin E, Vassilevski A. Design of sodium channel ligands with defined selectivity - a case study in scorpion alpha-toxins. FEBS Lett. 2017;591:3414-3420 pubmed publisher
    ..2 isoform expressed in the brain. ..

More Information


  1. Yoshida H, Nishi N, Wada K, Nakamura T, Hirashima M, Kuwabara N, et al. X-ray structure of a protease-resistant mutant form of human galectin-9 having two carbohydrate recognition domains with a metal-binding site. Biochem Biophys Res Commun. 2017;490:1287-1293 pubmed publisher
    ..This was supported by structural comparisons with other tandem-repeated galectins and the analyses of protein thermostability by CD spectra measurements. ..
  2. Perell G, Staebell R, Hairani M, Cembran A, Pomerantz W. Tuning Sulfur Oxidation States on Thioether-Bridged Peptide Macrocycles for Modulation of Protein Interactions. Chembiochem. 2017;18:1836-1844 pubmed publisher
    ..In some cases, proteolytic stability, binding capacity with KIX, and increased helicity were obtained as first steps toward developing PPI inhibitors. ..
  3. Pradhan S, Khatlani T, Nairn A, Vijayan K. The heterotrimeric G protein G?1 interacts with the catalytic subunit of protein phosphatase 1 and modulates G protein-coupled receptor signaling in platelets. J Biol Chem. 2017;292:13133-13142 pubmed publisher
    ..These findings suggest that G?1 protein enlists PP1c to modulate GPCR signaling in platelets. ..
  4. Loiseau L, Fyfe C, Aussel L, Hajj Chehade M, Hernández S, Faivre B, et al. The UbiK protein is an accessory factor necessary for bacterial ubiquinone (UQ) biosynthesis and forms a complex with the UQ biogenesis factor UbiJ. J Biol Chem. 2017;292:11937-11950 pubmed publisher
  5. Laiseca J, Ladelfa M, Cotignola J, Peche L, Pascucci F, Castaño B, et al. Functional interaction between co-expressed MAGE-A proteins. PLoS ONE. 2017;12:e0178370 pubmed publisher
    ..Overall, our results highlight the complexity of the MAGE gene networking in regulating cancer cell behavior. ..
  6. Henning L, Santos K, Sticht J, Jehle S, Lee C, Wittwer M, et al. A new role for FBP21 as regulator of Brr2 helicase activity. Nucleic Acids Res. 2017;45:7922-7937 pubmed publisher
    ..Furthermore, the direct interaction between FBP21 and the U4/U6 di-snRNA was found to reduce the pool of unwound U4/U6 di-snRNA. Our results suggest FBP21 as a novel key player in the regulation of Brr2. ..
  7. Zhao C, Ling B, Dong L, Liu Y. Theoretical insights into the protonation states of active site cysteine and citrullination mechanism of Porphyromonas gingivalis peptidylarginine deiminase. Proteins. 2017;85:1518-1528 pubmed publisher
    ..In view of the sequence similarity, these findings may be shared with human PAD1-PAD4 and other guanidino-group-modifying enzymes. Proteins 2017; 85:1518-1528. © 2017 Wiley Periodicals, Inc. ..
  8. Caing Carlsson R, Goyal P, Sharma A, Ghosh S, Setty T, North R, et al. Crystal structure of N-acetylmannosamine kinase from Fusobacterium nucleatum. Acta Crystallogr F Struct Biol Commun. 2017;73:356-362 pubmed publisher
    ..Unlike other NanK enzymes and ROK family members, F. nucleatum NanK does not have a conserved zinc-binding site. In spite of the absence of the zinc-binding site, all of the major structural features of enzymatic activity are conserved. ..
  9. Brogie J, Price D. Reconstitution of a functional 7SK snRNP. Nucleic Acids Res. 2017;45:6864-6880 pubmed publisher
    ..Inhibition of MEPCE is dependent on the structure of the 3? stem loop and the closed form of 7SK RNA. This study provides important insights into intramolecular interactions within the 7SK snRNP...
  10. McCullough J, Sundquist W. Putting a finger in the ring. Nat Struct Mol Biol. 2014;21:1025-7 pubmed publisher
  11. Borgel J, Tyl M, Schiller K, Pusztai Z, Dooley C, Deng W, et al. KDM2A integrates DNA and histone modification signals through a CXXC/PHD module and direct interaction with HP1. Nucleic Acids Res. 2017;45:1114-1129 pubmed publisher
    ..Our results reveal a complex regulation of chromatin binding for both KDM2A and HP1 that is modulated by DNA- and H3K9-methylation, and suggest a direct role for KDM2A in chromatin silencing. ..
  12. Beyersdorf M, Sircar R, Lookadoo D, Bottone C, Lynch M, Crane B, et al. Production, characterization, and assessment of a stable analog of the response regulator CheY-phosphate from Thermotoga maritima. Protein Sci. 2017;26:1547-1554 pubmed publisher
    ..Taken together these results suggest that Tm phosphono-CheY is a useful and unique analog of Tm CheY-phosphate. ..
  13. Robert Paganin J, Halladjian M, Blaud M, Lebaron S, Delbos L, Chardon F, et al. Functional link between DEAH/RHA helicase Prp43 activation and ATP base binding. Nucleic Acids Res. 2017;45:1539-1552 pubmed publisher
    ..Overall we propose that the stacking between the R- and F-motifs and the nucleotide base is important for the activity and regulation of this helicase family. ..
  14. Coates K, Walsh T, Spencer J, Hinchliffe P. 1.12?Å resolution crystal structure of the catalytic domain of the plasmid-mediated colistin resistance determinant MCR-2. Acta Crystallogr F Struct Biol Commun. 2017;73:443-449 pubmed publisher
    ..Variable amino acids are located distant from both the di-zinc active site and the membrane-proximal face. The exceptionally high resolution will provide an accurate starting model for further mechanistic studies...
  15. Fettelschoss V, Burda P, Sagné C, Coelho D, De Laet C, Lutz S, et al. Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B12-trafficking proteins ABCD4 and LMBD1. J Biol Chem. 2017;292:11980-11991 pubmed publisher
  16. Gerth M, Liu Y, Jiao W, Zhang X, Baker E, Lott J, et al. Crystal structure of a bicupin protein HutD involved in histidine utilization in Pseudomonas. Proteins. 2017;85:1580-1588 pubmed publisher
    ..74 Å resolution in several crystallization conditions, and identified N-formyl-l-glutamate (FG, a Hut pathway intermediate) as a potential ligand in vivo. Proteins 2017; 85:1580-1588. © 2017 Wiley Periodicals, Inc. ..
  17. Quach H, Tanigaki R, Yokoigawa J, Yamada Y, Niwa M, Hirano S, et al. Allantopyrone A interferes with multiple components of the TNF receptor 1 complex and blocks RIP1 modifications in the TNF-?-induced signaling pathway. J Antibiot (Tokyo). 2017;70:929-936 pubmed publisher
    ..The present results demonstrate that allantopyrone A interferes with multiple components of the TNF-R1 complex and blocks RIP1 modifications in the TNF-?-induced NF-?B signaling pathway. ..
  18. Qiu Y, Levendosky R, Chakravarthy S, Patel A, Bowman G, Myong S. The Chd1 Chromatin Remodeler Shifts Nucleosomal DNA Bidirectionally as a Monomer. Mol Cell. 2017;68:76-88.e6 pubmed publisher
    ..We propose that active interplay of the ATPase motor with the regulatory domains may promote dynamic nucleosome structures uniquely suited for histone exchange and chromatin reorganization during transcription. ..
  19. Xia Y, Shang Y, Zhang R, Zhu J. Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain. Biochem J. 2017;474:2817-2828 pubmed publisher
    ..Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs. ..
  20. Christian W, Hinkle P. Global functions of extracellular, transmembrane and cytoplasmic domains of organic solute transporter ?-subunit. Biochem J. 2017;474:1981-1992 pubmed publisher
    ..These results provide new insights into the structure and function of the heteromeric Ost transporter complex. ..
  21. Jiang L, Xiong J, Zhan J, Yuan F, Tang M, Zhang C, et al. Ubiquitin-specific peptidase 7 (USP7)-mediated deubiquitination of the histone deacetylase SIRT7 regulates gluconeogenesis. J Biol Chem. 2017;292:13296-13311 pubmed publisher
    ..In summary, SIRT7 is a USP7 substrate and has a novel role as a regulator of gluconeogenesis. Our study may provide the basis for new clinical approaches to treat metabolic disorders related to glucose metabolism. ..
  22. Khaliullin B, Ayikpoe R, Tuttle M, Latham J. Mechanistic elucidation of the mycofactocin-biosynthetic radical S-adenosylmethionine protein, MftC. J Biol Chem. 2017;292:13022-13033 pubmed publisher
    ..The finding that MftA* is the major product formed during MftC catalysis could have implications for the further elucidation of mycofactocin biosynthesis. ..
  23. Scaglione A, Fullone M, Montemiglio L, Parisi G, Zamparelli C, Vallone B, et al. Structure of the adenylation domain Thr1 involved in the biosynthesis of 4-chlorothreonine in Streptomyces sp. OH-5093-protein flexibility and molecular bases of substrate specificity. FEBS J. 2017;284:2981-2999 pubmed publisher
    ..Structural data are available in the Protein Data Bank under the accession number 5N9W and 5N9X. ..
  24. Kampatsikas I, Bijelic A, Pretzler M, Rompel A. In crystallo activity tests with latent apple tyrosinase and two mutants reveal the importance of the mutated sites for polyphenol oxidase activity. Acta Crystallogr F Struct Biol Commun. 2017;73:491-499 pubmed publisher
    ..The effects of the mutation on the activity of the enzyme were observed by colour changes of the crystals owing to the conversion of the substrates to dark chromophore products. ..
  25. Ishchenko Y, Novosolova N, Khafizov K, Bart G, Timonina A, Fayuk D, et al. Reconstructed Serine 288 in the Left Flipper Region of the Rat P2X7 Receptor Stabilizes Nonsensitized States. Biochemistry. 2017;56:3394-3402 pubmed publisher
    ..Our combined experimental, kinetic, and molecular modeling data suggest that the rat F288S novel phenotype is due to a slower rate of ATP binding and/or unbinding and stabilization of nonsensitized receptor states. ..
  26. Upadhyay A, Cyr M, Longenecker K, Tripathi R, Sun C, Kempf D. Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5. Acta Crystallogr F Struct Biol Commun. 2017;73:116-122 pubmed publisher
    ..The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain. ..
  27. Singh A, Ekka M, Kaushik A, Pandya V, Singh R, Banerjee S, et al. Substrate-Induced Facilitated Dissociation of the Competitive Inhibitor from the Active Site of O-Acetyl Serine Sulfhydrylase Reveals a Competitive-Allostery Mechanism. Biochemistry. 2017;56:5011-5025 pubmed publisher
  28. Uversky V. Intrinsic disorder here, there, and everywhere, and nowhere to escape from it. Cell Mol Life Sci. 2017;74:3065-3067 pubmed publisher
  29. Sahu S, Weirick T, Kaundal R. Predicting genome-scale Arabidopsis-Pseudomonas syringae interactome using domain and interolog-based approaches. BMC Bioinformatics. 2014;15 Suppl 11:S13 pubmed publisher
    ..This can be a useful resource to the plant community to characterize the host-pathogen interaction in Arabidopsis and Pseudomonas system. Further, these prediction models can be applied to the agriculturally relevant crops. ..
  30. Basilico C, Hultberg A, Blanchetot C, De Jonge N, Festjens E, Hanssens V, et al. Four individually druggable MET hotspots mediate HGF-driven tumor progression. J Clin Invest. 2014;124:3172-86 pubmed publisher
    ..These results identify multiple regions of MET responsible for HGF-mediated tumor progression, unraveling the complexity of HGF-MET interaction, and provide selective molecular tools for targeting MET activity in cancer. ..
  31. Ottmann C. Small-molecule modulation of protein-protein interactions. Drug Discov Today Technol. 2013;10:e499-500 pubmed publisher
  32. Waraky A, Lin Y, Warsito D, Haglund F, Aleem E, Larsson O. Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage. J Biol Chem. 2017;292:18227-18239 pubmed publisher
    ..Unlike in cells expressing IGF-1R, externally induced DNA damage in IGF-1R-negative cells caused G1 cell cycle arrest and S phase fork stalling. Taken together, our results suggest a role of IGF-1R in DDT. ..
  33. Andreatta M, Jurtz V, Kaever T, Sette A, Peters B, Nielsen M. Machine learning reveals a non-canonical mode of peptide binding to MHC class II molecules. Immunology. 2017;152:255-264 pubmed publisher
    ..This previously undescribed mode of peptide binding to MHCII molecules gives a more complete picture of peptide presentation by MHCII and allows us to model more accurately this event. ..
  34. Mahmoud M, Schechter A, Alnajjar K, Huang J, Towle Weicksel J, Eckenroth B, et al. Defective Nucleotide Release by DNA Polymerase β Mutator Variant E288K Is the Basis of Its Low Fidelity. Biochemistry. 2017;56:5550-5559 pubmed publisher
    ..Structural modeling implies that this inherent defect is due to interaction of E288K with DNA, resulting in a stable closed enzyme structure. ..
  35. Kii I, Ito H. Periostin and its interacting proteins in the construction of extracellular architectures. Cell Mol Life Sci. 2017;74:4269-4277 pubmed publisher
  36. Krishnamohan A, Jackman J. Mechanistic features of the atypical tRNA m1G9 SPOUT methyltransferase, Trm10. Nucleic Acids Res. 2017;45:9019-9029 pubmed publisher
    ..These results provide evidence for a non-canonical tRNA methyltransferase mechanism that characterizes the Trm10 enzyme family. ..
  37. Oda T, Hirabayashi H, Shikauchi G, Takamura R, Hiraga K, Minami H, et al. Structural basis of autoinhibition and activation of the DNA-targeting ADP-ribosyltransferase pierisin-1. J Biol Chem. 2017;292:15445-15455 pubmed publisher
    ..Our study provides a structural basis for the DNA-acceptor specificity of pierisin-1 and reveals that a self-regulatory mechanism is required for its activity. ..
  38. Davies A, Allan E, Keeble A, Delgado J, Cossins B, Mitropoulou A, et al. Allosteric mechanism of action of the therapeutic anti-IgE antibody omalizumab. J Biol Chem. 2017;292:9975-9987 pubmed publisher
  39. Qasem Abdullah H, Perach M, Livnat Levanon N, Lewinson O. ATP binding and hydrolysis disrupt the high-affinity interaction between the heme ABC transporter HmuUV and its cognate substrate-binding protein. J Biol Chem. 2017;292:14617-14624 pubmed publisher
    ..Subsequent ATP hydrolysis leads to substrate delivery to the cytoplasm, release of the SBP, and resetting of the system. We propose that other Type II ABC transporters likely share the fundamentals of this mechanism. ..
  40. Gangula N, Maddika S. Interplay between the phosphatase PHLPP1 and E3 ligase RNF41 stimulates proper kinetochore assembly via the outer-kinetochore protein SGT1. J Biol Chem. 2017;292:13947-13958 pubmed publisher
    ..Taken together, our results suggest that PHLPP1 plays an important role in the assembly of kinetochores by counteracting RNF41-mediated SGT1 degradation. ..
  41. Shaik M, Bhattacharjee N, Feliks M, Ng K, Field M. Norovirus RNA-dependent RNA polymerase: A computational study of metal-binding preferences. Proteins. 2017;85:1435-1445 pubmed publisher
    ..The highest binding energy is for copper, followed closely by manganese and iron, and then by zinc, nickel, and cobalt. Proteins 2017; 85:1435-1445. © 2017 Wiley Periodicals, Inc. ..
  42. Mina J, Thye J, Alqaisi A, Bird L, Dods R, Grøftehauge M, et al. Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites. J Biol Chem. 2017;292:12208-12219 pubmed publisher
    ..Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote. ..
  43. Frenkel Morgenstern M, Gorohovski A, Tagore S, Sekar V, Vazquez M, Valencia A. ChiPPI: a novel method for mapping chimeric protein-protein interactions uncovers selection principles of protein fusion events in cancer. Nucleic Acids Res. 2017;45:7094-7105 pubmed publisher
    ..Thus, the ChiPPI method represents a comprehensive tool for studying the anomaly of skewed cellular networks produced by fusion proteins in cancer. ..
  44. Ershov P, Yablokov E, Mezentsev Y, Kalushskiy L, Florinskaya A, Veselovsky A, et al. [The effect of isatin on protein-protein interactions between cytochrome b5 and cytochromes P450]. Biomed Khim. 2017;63:170-175 pubmed publisher
    ..Po dannym molekuliarnogo dokinga izatin mozhet vliiat' na vzaimode?stvie CYP3A5 ili CYP3A4 s CYB5A za schet sviazyvaniia v oblasti kontakta CYB5A/CYP. ..
  45. Zhang Z, Ohto U, Shimizu T. Toward a structural understanding of nucleic acid-sensing Toll-like receptors in the innate immune system. FEBS Lett. 2017;591:3167-3181 pubmed publisher
    ..This Review summarizes the novel structural understanding of NA-sensing by TLRs and regulatory mechanisms of these receptors. ..
  46. Shrestha P, Yun J, Ko Y, Yeon K, Kim D, Lee H, et al. NMR uncovers direct interaction between human NEDD4-1 and p34SEI-1. Biochem Biophys Res Commun. 2017;490:984-990 pubmed publisher
    ..Our data will provide insights into the molecular mechanism of NEDD4-1 and p34SEI-1 interaction, which will be directly used for drug design which inhibits the molecular interaction involved in different cancer signaling. ..
  47. Marunaka K, Furukawa C, Fujii N, Kimura T, Furuta T, Matsunaga T, et al. The RING finger- and PDZ domain-containing protein PDZRN3 controls localization of the Mg2+ regulator claudin-16 in renal tube epithelial cells. J Biol Chem. 2017;292:13034-13044 pubmed publisher
    ..These results suggest that PDZRN3 mediates endocytosis of dephosphorylated CLDN16 and represents an important component of the CLDN16-trafficking machinery in the kidney. ..
  48. Zanotti S, Yu J, Sanjay A, Schilling L, Schoenherr C, Economides A, et al. Sustained Notch2 signaling in osteoblasts, but not in osteoclasts, is linked to osteopenia in a mouse model of Hajdu-Cheney syndrome. J Biol Chem. 2017;292:12232-12244 pubmed publisher
    ..In conclusion, introduction of the HCS mutation in osteoblasts, but not in osteoclasts, causes osteopenia. ..
  49. Kanaki M, Tiniakou I, Thymiakou E, Kardassis D. Physical and functional interactions between nuclear receptor LXR? and the forkhead box transcription factor FOXA2 regulate the response of the human lipoprotein lipase gene to oxysterols in hepatic cells. Biochim Biophys Acta Gene Regul Mech. 2017;1860:848-860 pubmed publisher
    ..This mechanism, which may not be restricted to the LPL gene, is critically important for a better understanding of the regulation of cholesterol and triglyceride metabolism in the liver under healthy or pathological states. ..
  50. Levy A, Turgeman M, Gevorkyan Aiapetov L, Ruthstein S. The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations. Protein Sci. 2017;26:1609-1618 pubmed publisher
    ..Our data provide insight regarding the structural mechanisms through which Atox1 can fulfill its dual role of copper binding and transfer. ..
  51. Oudouhou F, Casu B, Dopgwa Puemi A, Sygusch J, Baron C. Analysis of Novel Interactions between Components of the Selenocysteine Biosynthesis Pathway, SEPHS1, SEPHS2, SEPSECS, and SECp43. Biochemistry. 2017;56:2261-2270 pubmed publisher
    ..The SECp43 structural model presented here constitutes the basis of future exploration of the protein-protein interactions among early components of the selenocysteine biosynthesis and incorporation pathway. ..
  52. Mullard A. Protein-protein interaction inhibitors get into the groove. Nat Rev Drug Discov. 2012;11:173-5 pubmed publisher
  53. Hsieh Y, Huang Y, Zhang H, Liu Q, Lu Y, Yang H, et al. Dissecting structures and functions of SecA-only protein-conducting channels: ATPase, pore structure, ion channel activity, protein translocation, and interaction with SecYEG/SecDF•YajC. PLoS ONE. 2017;12:e0178307 pubmed publisher