- •Modular structure of proteins
- •Structural domains
- •The evolution and shuffling of domains
- •Sequence homology and the acquisition of function
- •Domain function
- •Catalytic domains
- •Protein interaction domains
- •The inventory of domains
- •Detection
- •Classification
- •Examples of domains with roles in signalling
- •Domains that bind oligopeptide motifs
- •SH2 domains
- •PTB domains
- •SH3 domains
- •Phosphoinositide-binding domains
- •PH domains
- •Other phosphoinositide-binding domains
- •Polypeptide modules that bind Ca2
- •Calcium-binding motifs and domains
- •The EF-hand motif
- •C2 domains
- •Zinc finger domains
- •Protein kinase domains
- •Protein kinases share a common domain
- •Structural elements that regulate kinase activity
- •References
Protein Domains and Signal Transduction
PKB |
protein kinase B (Akt) |
|
|
PKA, PKC |
protein kinase A, protein kinase C |
|
|
PLC- |
phospholipase C |
|
|
PLC- |
phospholipase C |
|
|
PLD |
phospholipase D |
|
|
P-rich |
proline-rich regions |
|
|
pS |
phosphoserine |
|
|
pT |
phosphothreonine |
|
|
pY |
phosphotyrosine |
|
|
RasGAP |
Ras GTPase activating protein |
|
|
RGS |
regulator of G protein signalling |
|
|
SARA |
Smad anchor for receptor activation |
|
|
Shc |
SH2-containing protein |
|
|
Smads |
transcription factors in TGF receptor family pathway |
|
|
Snf-2 |
Transcriptional coactivator |
|
|
Sos |
Ras guanine nucleotide exchange factor |
|
|
Src |
Src tyrosine kinase |
|
|
STATS |
signal transducers and activators of transcription |
|
|
STE4 |
yeast G of pheromone pathway |
|
|
Swi-2 |
transcriptional coactivator |
|
|
Syt |
synaptotagmin |
|
|
TFIID complex |
transcription factor IID complex |
|
|
TNF |
tumour necrosis factor |
|
|
TRADD |
TNF-associated protein with death domain |
|
|
Vav |
adaptor protein and Rho GEF |
|
|
References
1.Lupas AN, Ponting CP, Russell RB. On the evolution of protein folds: are similar motifs in different protein folds the result of convergence, insertion, or relics of an ancient peptide world?. J Struct Biol. 2001;134:191–203.
787
Signal Transduction
2. Liu M, Grigoriev A. Protein domains correlate strongly with exons in multiple eukaryotic genomes – evidence of exon shuffling? Trends Genet 2004;20:399–403.
3. Graur D, Li W-H. Fundamentals of Molecular Evolution. pp. 1–439. Sunderland, MA: Sinauer Associates; 2000.
4. Pawson T, Nash P. Assembly of cell regulatory systems through protein interaction domains. Science. 2003;300:445–452.
5. Finn RD, Mistry J, Schuster-Bockler B, et al. Pfam: clans, web tools and services. Nucleic Acids Res. 2006;34:D247–D251.
6. Sadowski I, Stone JC, Pawson T. A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps. Mol Cell Biol. 2006;6:4396–4408.
7. Liu BA, Jablonowski K, Raina M, Arce M, Pawson T, Nash PD. The human and mouse complement of SH2 domain proteins-establishing the boundaries of phosphotyrosine signaling. Mol Cell. 2006;22:851–868.
8. Fukuzawa M, Araki T, Adrian I, Williams JG. Tyrosine phosphorylationindependent nuclear translocation of a dictyostelium STAT in response to DIF signaling. Mol Cell. 2001;7:779–788.
9. King N, Hittinger CT, Carroll SB. Evolution of key cell signaling and adhesion protein families predates animal origins. Science. 2006; 301:361–363.
10.Eck MJ, Shoelson SE, Harrison SC. Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck. Nature. 1993;362:87–91.
11.Kimber MS, Nachman J, Cunningham AM, Gish GD, Pawson T, Pai EF. Structural basis for specificity switching of the Src SH2 domain. Mol Cell. 2000;5:1043–1049.
12.Songyang Z, Margolis B, Chaudhuri M, Shoelson SE, Cantley LC. The phosphotyrosine interaction domain of SHC recognizes tyrosinephosphorylated NPXY motif. J Biol Chem. 1995;270:14863–14866.
13.Zhou MM, Huang B, Olejniczak ET, et al. Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain. Nat Struct Biol. 1996;3:388–393.
14.Uhlik MT, Temple B, Bencharit S, Kimple AJ, Siderovski DP, Johnson GL. Structural and evolutionary division of phosphotyrosine binding (PTB) domains. J Mol Biol. 2006;345:1–20.
15.Renzoni DA, Pugh DJ, Siligardi G, et al. Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase. Biochemistry. 1996;35:15646–15653.
16.Yu H, Rosen MK, Shin TB, Seidel Dugan C, Brugge JS, Schreiber SL. Solution structure of the SH3 domain of Src and identification of its ligand-binding site. Science. 1992;258:1665–1668.
788
Protein Domains and Signal Transduction
17.Hu KQ, Settleman J. Tandem SH2 binding sites mediate the RasGAPRhoGAP interaction: a conformational mechanism for SH3 domain regulation. EMBO J. 1997;16:473–483.
18.Lemmon MA. Phosphoinositide recognition domains. Traffic. 2003;4: 201–213.
19.Takenawa T, Itoh T. Membrane targeting and remodeling through phosphoinositide-binding domains. IUBMB Life. 2006;58:296–303.
20.Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.
21.Lemmon MA. Pleckstrin homology domains: not just for phosphoinositides. Biochem Soc Trans. 2004;32:707–711.
22.Haslam RJ, Koide HB, Hemmings BA. Pleckstrin domain homology. Nature. 1993;363:309–310.
23.Imaoka T, Lynham JA, Haslam RJ. Purification and characterization of the 47,000-dalton protein phosphorylated during degranulation of human platelets. J Biol Chem. 1983;258:11404–11414.
24.Lemmon MA, Ferguson KM, O’Brien R, Sigler PB, Schlessinger J. Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain. Proc Natl Acad Sci USA. 1995;92:10472–10476.
25.Flesch FM, Yu JW, Lemmon MA, Burger KN. Membrane activity of the phospholipase C- 1 pleckstrin homology (PH) domain. Biochem
J. 2005;389:435–441.
26.Tesmer VM, Kawano T, Shankaranarayanan A, Kozasa T, Tesmer JJ. Snapshot of activated G proteins at the membrane: the G q-GRK2-G complex. Science. 2005;310:1686–1690.
27.Ferguson KM, Lemmon MA, Schlessinger J, Sigler PB. Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain. Cell. 1995;83:1037–1046.
28.Di Paolo G, De Camilli P. Phosphoinositides in cell regulation and membrane dynamics. Nature. 2006;443:651–657.
29.Mu FT, Callaghan JM, Steele-Mortimer O, et al. EEA1, an early endosomeassociated protein. EEA1 is a conserved -helical peripheral membrane protein flanked by cysteine ‘fingers’ and contains a calmodulin-binding IQ motif,. J Biol Chem. 1995;270:13503–13511.
30.Gaullier JM, Simonsen A, D’Arrigo A, Bremnes B, Stenmark H, Aasland R. FYVE fingers bind PtdIns(3)P. Nature. 1998;394:432–433.
31.Simonsen A, Lippe R, Christoforidis S, et al. EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature. 1998;394:494–498.
32.Kutateladze T, Overduin M. Structural mechanism of endosome docking by the FYVE domain. Science. 2001;291:1793–1796.
33.Segal AW. How neutrophils kill microbes. Annu Rev Immunol. 2005;23:197–223.
34.Chen H, Fre S, Slepnev VI, et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature. 1998;394:793–797.
789
Signal Transduction
35.Kretsinger RH. Calcium-binding proteins. Annu Rev Biochem. 1976;45: 239–266.
36.Babu YS, Sack JS, Greenhough TJ, Bugg CE, Means AR, Cook WJ. Threedimensional structure of calmodulin. Nature. 1985;315:37–40.
37.Chattopadhyaya R, Meador WE, Means AR, Quiocho FA. Calmodulin structure refined at 1.7 Ångstrom resolution. J Mol Biol. 1992;228:1177–1192.
38.Ubach J, Zhang X, Shao X, Südhof TC, Rizo J. Ca2 binding to synaptotagmin: how many Ca2 ions bind to the tip of a C2-domain? EMBO J. 1998;17:3921–3930.
39.Verdaguer N, Corbalan-Garcia S, Ochoa WF, Fita I, Gomez-Fernandez JC. Ca2 bridges the C2 membrane-binding domain of protein kinase C directly to phosphatidylserine. EMBO J. 1999;18:6329–6338.
40.Corbalan-Garcia S, Garcia-Garcia J, Rodriguez-Alfaro JA, GomezFernandez JC. A new phosphatidylinositol 4,5-bisphosphate-binding site located in the C2 domain of protein kinase C . J Biol Chem. 2003;278:4972–4980.
41.Sutton RB, Sprang SR. Structure of the protein kinase C phospholipidbinding C2 domain complexed with Ca2 . Structure. 1998;6:1395–1405.
42.Miller J, McLachlan AD, Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985;4:1609–1614.
43.Matthews JM, Sunde M. Zinc fingers – folds for many occasions. IUBMB Life. 2002;54:351–355.
44.Li J, Chen X, Yang H, et al. The zinc finger transcription factor 191 is required for early embryonic development and cell proliferation. Exp Cell Res. 2006;312:3990–3998.
45.Sato M, Tomizawa T, Koshiba S, Inoue M, Kigawa T, Yokoyama S. Solution structures of the C2H2 type zinc finger domain of human Zinc finger protein 24. Deposited RCSB 2005. To be published.
46.Xu RX, Pawelczyk T, Xia TH, Brown SC. NMR structure of a protein kinase C- phorbol-binding domain and study of protein-lipid micelle interactions. Biochemistry. 1997;36:10709–10717.
47.Ono Y, Fujii T, Igarashi K, et al. Phorbol ester binding to protein kinase C requires a cysteine-rich zinc finger-like sequence. Proc Natl Acad Sci USA. 1989;86:4868–4871.
48.Johnson LN, Noble ME, Owen DJ. Active and inactive protein kinases: structural basis for regulation. Cell. 1996;85:149–158.
49.Bossemeyer D, Engh RA, Kinzel V, Ponstingl H, Huber R. Phosphotransferase and substrate binding mechanism of the cAMPdependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 Å structure of the complex with Mn2 adenylyl imidodiphosphate and inhibitor peptide PKI(5-24). EMBO J. 1993;12:859.
790
