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PDBsum entry 1sko

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protein Protein-protein interface(s) links
Signaling protein PDB id
1sko
Jmol
Contents
Protein chains
119 a.a. *
116 a.a. *
Waters ×230
* Residue conservation analysis
PDB id:
1sko
Name: Signaling protein
Title: Mp1-p14 complex
Structure: Mitogen-activated protein kinase kinase 1 interacting protein 1. Chain: a. Synonym: mek binding partner 1, mp1, pro2783. Engineered: yes. Late endosomal/lysosomal mp1 interacting protein. Chain: b. Synonym: p14. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: map2k1ip1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Mus musculus. House mouse. Organism_taxid: 10090.
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.205     R-free:   0.271
Authors: V.V.Lunin,C.Munger,J.Wagner,Z.Ye,M.Cygler,M.Sacher
Key ref:
V.V.Lunin et al. (2004). The structure of the MAPK scaffold, MP1, bound to its partner, p14. A complex with a critical role in endosomal map kinase signaling. J Biol Chem, 279, 23422-23430. PubMed id: 15016825 DOI: 10.1074/jbc.M401648200
Date:
05-Mar-04     Release date:   01-Jun-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9UHA4  (LTOR3_HUMAN) -  Ragulator complex protein LAMTOR3
Seq:
Struc:
124 a.a.
119 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9JHS3  (LTOR2_MOUSE) -  Ragulator complex protein LAMTOR2
Seq:
Struc:
125 a.a.
116 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     Ragulator complex   9 terms 
  Biological process     cellular response to amino acid stimulus   8 terms 
  Biochemical function     protein binding     3 terms  

 

 
DOI no: 10.1074/jbc.M401648200 J Biol Chem 279:23422-23430 (2004)
PubMed id: 15016825  
 
 
The structure of the MAPK scaffold, MP1, bound to its partner, p14. A complex with a critical role in endosomal map kinase signaling.
V.V.Lunin, C.Munger, J.Wagner, Z.Ye, M.Cygler, M.Sacher.
 
  ABSTRACT  
 
Scaffold proteins of the mitogen-activated protein kinase (MAPK) pathway have been proposed to form an active signaling module and enhance the specificity of the transduced signal. Here, we report a 2-A resolution structure of the MAPK scaffold protein MP1 in a complex with its partner protein, p14, that localizes the complex to late endosomes. The structures of these two proteins are remarkably similar, with a five-stranded beta-sheet flanked on either side by a total of three helices. The proteins form a heterodimer in solution and interact mainly through the edge beta-strand in each protein to generate a 10-stranded beta-sheet core. Both proteins also share structural similarity with the amino-terminal regulatory domains of the membrane trafficking proteins, sec22b and Ykt6p, as well as with sedlin (a component of a Golgi-associated membrane-trafficking complex) and the sigma2 and amino-terminal portion of the mu2 subunits of the clathrin adaptor complex AP2. Because neither MP1 nor p14 have been implicated in membrane traffic, we propose that the similar protein folds allow these relatively small proteins to be involved in multiple and simultaneous protein-protein interactions. Mapping of highly conserved, surface-exposed residues on MP1 and p14 provided insight into the potential sites of binding of the signaling kinases MEK1 and ERK1 to this complex, as well as the areas potentially involved in other protein-protein interactions.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. The structure of the MP1-p14 complex. A, stereo view of the ribbon drawing of the MP1-p14 complex. MP1 is painted yellow, and p14 is painted blue. Superimposed on the ribbon is a semitransparent molecular surface of the complex with the exclusion of helices 2 of both MP1 and p14. Loops lining the canyon walls are shown in orange (MP1) and magenta (p14). The figure was rendered with PyMol (DeLano Scientific; www.pymol.org). Folding diagrams of MP1 (B) and p14 (C) are shown. The five -strands and three -helices are shown. In MP1, 2' indicates a five-residue helical twist from Pro42 to Leu46.
Figure 3.
FIG. 3. The MP1-p14 interface. Stereo view of the MP1-p14 interface. The main chain and carbon atoms of MP1 and p14 are colored yellow and green, respectively. The side chains are colored by atom type for non-carbon atoms. Dashed lines show the intermolecular hydrogen bonds between MP1 and p14. N and C termini of main chain fragments are labeled with residue numbers. The figure was rendered with Molscript (53) and Raster3D (54).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 23422-23430) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23361334 J.L.Jewell, R.C.Russell, and K.L.Guan (2013).
Amino acid signalling upstream of mTOR.
  Nat Rev Mol Cell Biol, 14, 133-139.  
20381137 Y.Sancak, L.Bar-Peled, R.Zoncu, A.L.Markhard, S.Nada, and D.M.Sabatini (2010).
Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.
  Cell, 141, 290-303.  
19289794 A.Lu, F.Tebar, B.Alvarez-Moya, C.López-Alcalá, M.Calvo, C.Enrich, N.Agell, T.Nakamura, M.Matsuda, and O.Bachs (2009).
A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes.
  J Cell Biol, 184, 863-879.  
18936176 A.M.deCathelineau, and G.M.Bokoch (2009).
Inactivation of rho GTPases by statins attenuates anthrax lethal toxin activity.
  Infect Immun, 77, 348-359.  
19177150 S.Nada, A.Hondo, A.Kasai, M.Koike, K.Saito, Y.Uchiyama, and M.Okada (2009).
The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes.
  EMBO J, 28, 477-489.  
17254543 A.Brahma, and K.N.Dalby (2007).
Regulation of protein phosphorylation within the MKK1-ERK2 complex by MP1 and the MP1*P14 heterodimer.
  Arch Biochem Biophys, 460, 85-91.  
17553668 A.K.Pullikuth, and A.D.Catling (2007).
Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: a perspective.
  Cell Signal, 19, 1621-1632.  
17689063 C.E.Au, A.W.Bell, A.Gilchrist, J.Hiding, T.Nilsson, and J.J.Bergeron (2007).
Organellar proteomics to create the cell map.
  Curr Opin Cell Biol, 19, 376-385.  
17206132 E.C.Dell'Angelica (2007).
Bad signals jam organelle traffic.
  Nat Med, 13, 31-32.  
16440056 K.K.Pfister, P.R.Shah, H.Hummerich, A.Russ, J.Cotton, A.A.Annuar, S.M.King, and E.M.Fisher (2006).
Genetic analysis of the cytoplasmic dynein subunit families.
  PLoS Genet, 2, e1.  
16543275 K.S.Makarova, E.V.Koonin, R.Haselkorn, and M.Y.Galperin (2006).
Cyanobacterial response regulator PatA contains a conserved N-terminal domain (PATAN) with an alpha-helical insertion.
  Bioinformatics, 22, 1297-1301.  
16837555 Y.Kapp-Barnea, L.Ninio-Many, K.Hirschberg, M.Fukuda, A.Jeromin, and R.Sagi-Eisenberg (2006).
Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta stimulate extracellular signal-regulated kinase 1/2 signaling by accelerating recycling through the endocytic recycling compartment.
  Mol Biol Cell, 17, 4130-4141.  
15923628 A.Pullikuth, E.McKinnon, H.J.Schaeffer, and A.D.Catling (2005).
The MEK1 scaffolding protein MP1 regulates cell spreading by integrating PAK1 and Rho signals.
  Mol Cell Biol, 25, 5119-5133.  
15547943 C.Sharma, T.Vomastek, A.Tarcsafalvi, A.D.Catling, H.J.Schaeffer, S.T.Eblen, and M.J.Weber (2005).
MEK partner 1 (MP1): regulation of oligomerization in MAP kinase signaling.
  J Cell Biochem, 94, 708-719.  
16262728 M.S.Kim, M.J.Yi, K.H.Lee, J.Wagner, C.Munger, Y.G.Kim, M.Whiteway, M.Cygler, B.H.Oh, and M.Sacher (2005).
Biochemical and crystallographic studies reveal a specific interaction between TRAPP subunits Trs33p and Bet3p.
  Traffic, 6, 1183-1195.
PDB code: 2c0j
15639316 R.A.Nixon (2005).
Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases.
  Neurobiol Aging, 26, 373-382.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.