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PDBsum entry 2k9j

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protein Protein-protein interface(s) links
Membrane protein PDB id
2k9j
Jmol
Contents
Protein chains
42 a.a. *
43 a.a. *
* Residue conservation analysis
PDB id:
2k9j
Name: Membrane protein
Title: Integrin alphaiib-beta3 transmembrane complex
Structure: Integrin alpha-iib light chain. Chain: a. Fragment: transmembrane domain. Engineered: yes. Integrin beta-3. Chain: b. Fragment: transmembrane domain. Synonym: platelet membrane glycoprotein iiia, gpiiia, cd61 engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: itga2b, gp2b, itgab. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: itgb3, gp3a.
NMR struc: 21 models
Authors: T.Lau,C.Kim,M.H.Ginsberg,T.S.Ulmer
Key ref: T.L.Lau et al. (2009). The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling. EMBO J, 28, 1351-1361. PubMed id: 19279667
Date:
15-Oct-08     Release date:   24-Mar-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08514  (ITA2B_HUMAN) -  Integrin alpha-IIb
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1039 a.a.
42 a.a.*
Protein chain
Pfam   ArchSchema ?
P05106  (ITB3_HUMAN) -  Integrin beta-3
Seq:
Struc:
 
Seq:
Struc:
788 a.a.
43 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integrin complex   1 term 
  Biological process     cell adhesion   7 terms 
  Biochemical function     receptor activity     1 term  

 

 
EMBO J 28:1351-1361 (2009)
PubMed id: 19279667  
 
 
The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling.
T.L.Lau, C.Kim, M.H.Ginsberg, T.S.Ulmer.
 
  ABSTRACT  
 
Heterodimeric integrin adhesion receptors regulate cell migration, survival and differentiation in metazoa by communicating signals bi-directionally across the plasma membrane. Protein engineering and mutagenesis studies have suggested that the dissociation of a complex formed by the single-pass transmembrane (TM) segments of the alpha and beta subunits is central to these signalling events. Here, we report the structure of the integrin alphaIIbbeta3 TM complex, structure-based site-directed mutagenesis and lipid embedding estimates to reveal the structural event that underlies the transition from associated to dissociated states, that is, TM signalling. The complex is stabilized by glycine-packing mediated TM helix crossing within the extracellular membrane leaflet, and by unique hydrophobic and electrostatic bridges in the intracellular leaflet that mediate an unusual, asymmetric association of the 24- and 29-residue alphaIIb and beta3 TM helices. The structurally unique, highly conserved integrin alphaIIbbeta3 TM complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22178926 C.Kim, T.Schmidt, E.G.Cho, F.Ye, T.S.Ulmer, and M.H.Ginsberg (2012).
Basic amino-acid side chains regulate transmembrane integrin signalling.
  Nature, 481, 209-213.
PDB code: 2l91
21216149 N.J.Anthis, and I.D.Campbell (2011).
The tail of integrin activation.
  Trends Biochem Sci, 36, 191-198.  
21087420 P.Pinon, and B.Wehrle-Haller (2011).
Integrins: versatile receptors controlling melanocyte adhesion, migration and proliferation.
  Pigment Cell Melanoma Res, 24, 282-294.  
20940419 S.Tadokoro, T.Nakazawa, T.Kamae, K.Kiyomizu, H.Kashiwagi, S.Honda, Y.Kanakura, and Y.Tomiyama (2011).
A potential role for α-actinin in inside-out αIIbβ3 signaling.
  Blood, 117, 250-258.  
20947017 A.C.Kalli, K.L.Wegener, B.T.Goult, N.J.Anthis, I.D.Campbell, and M.S.Sansom (2010).
The structure of the talin/integrin complex at a lipid bilayer: an NMR and MD simulation study.
  Structure, 18, 1280-1288.  
19897481 A.Nogales, C.García, J.Pérez, P.Callow, T.A.Ezquerra, and J.González-Rodríguez (2010).
Three-dimensional model of human platelet integrin alphaIIb beta3 in solution obtained by small angle neutron scattering.
  J Biol Chem, 285, 1023-1031.  
20610383 A.R.Gingras, N.Bate, B.T.Goult, B.Patel, P.M.Kopp, J.Emsley, I.L.Barsukov, G.C.Roberts, and D.R.Critchley (2010).
Central region of talin has a unique fold that binds vinculin and actin.
  J Biol Chem, 285, 29577-29587.
PDB code: 2x0c
20150896 B.T.Goult, M.Bouaouina, P.R.Elliott, N.Bate, B.Patel, A.R.Gingras, J.G.Grossmann, G.C.Roberts, D.A.Calderwood, D.R.Critchley, and I.L.Barsukov (2010).
Structure of a double ubiquitin-like domain in the talin head: a role in integrin activation.
  EMBO J, 29, 1069-1080.
PDB codes: 2kc1 2kc2 2kma
20584077 C.Rosano, and M.Rocco (2010).
Solution properties of full-length integrin alpha(IIb)beta3 refined models suggest environment-dependent induction of alternative bent /extended resting states.
  FEBS J, 277, 3190-3202.  
20033057 C.Xie, J.Zhu, X.Chen, L.Mi, N.Nishida, and T.A.Springer (2010).
Structure of an integrin with an alphaI domain, complement receptor type 4.
  EMBO J, 29, 666-679.
PDB codes: 3k6s 3k71 3k72
21156831 D.G.Metcalf, D.T.Moore, Y.Wu, J.M.Kielec, K.Molnar, K.G.Valentine, A.J.Wand, J.S.Bennett, and W.F.DeGrado (2010).
NMR analysis of the alphaIIb beta3 cytoplasmic interaction suggests a mechanism for integrin regulation.
  Proc Natl Acad Sci U S A, 107, 22481-22486.
PDB code: 2kv9
  20421711 E.V.Bocharov, P.E.Volynsky, K.V.Pavlov, R.G.Efremov, and A.S.Arseniev (2010).
Structure elucidation of dimeric transmembrane domains of bitopic proteins.
  Cell Adh Migr, 4, 284-298.  
20048261 F.Ye, G.Hu, D.Taylor, B.Ratnikov, A.A.Bobkov, M.A.McLean, S.G.Sligar, K.A.Taylor, and M.H.Ginsberg (2010).
Recreation of the terminal events in physiological integrin activation.
  J Cell Biol, 188, 157-173.  
20665668 J.Lim, A.G.Dupuy, D.R.Critchley, and E.Caron (2010).
Rap1 controls activation of the α(M)β(2) integrin in a talin-dependent manner.
  J Cell Biochem, 111, 999.  
20802519 J.Nevo, A.Mai, S.Tuomi, T.Pellinen, O.T.Pentikäinen, P.Heikkilä, J.Lundin, H.Joensuu, P.Bono, and J.Ivaska (2010).
Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion.
  Oncogene, 29, 6452-6463.  
19693543 M.Barczyk, S.Carracedo, and D.Gullberg (2010).
Integrins.
  Cell Tissue Res, 339, 269-280.  
21134635 M.E.Call, and J.J.Chou (2010).
A view into the blind spot: solution NMR provides new insights into signal transduction across the lipid bilayer.
  Structure, 18, 1559-1569.  
20336801 M.G.Wolf, M.Hoefling, C.Aponte-Santamaría, H.Grubmüller, and G.Groenhof (2010).
g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation.
  J Comput Chem, 31, 2169-2174.  
21134644 N.J.Anthis, K.L.Wegener, D.R.Critchley, and I.D.Campbell (2010).
Structural diversity in integrin/talin interactions.
  Structure, 18, 1654-1666.  
  20543559 P.Hubert, P.Sawma, J.P.Duneau, J.Khao, J.Hénin, D.Bagnard, and J.Sturgis (2010).
Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?
  Cell Adh Migr, 4, 313-324.  
20947018 P.R.Elliott, B.T.Goult, P.M.Kopp, N.Bate, J.G.Grossmann, G.C.Roberts, D.R.Critchley, and I.L.Barsukov (2010).
The Structure of the talin head reveals a novel extended conformation of the FERM domain.
  Structure, 18, 1289-1299.
PDB code: 3ivf
20308986 S.J.Shattil, C.Kim, and M.H.Ginsberg (2010).
The final steps of integrin activation: the end game.
  Nat Rev Mol Cell Biol, 11, 288-300.  
20570504 T.Raschle, S.Hiller, M.Etzkorn, and G.Wagner (2010).
Nonmicellar systems for solution NMR spectroscopy of membrane proteins.
  Curr Opin Struct Biol, 20, 471-479.  
  20168080 T.S.Ulmer (2010).
Structural basis of transmembrane domain interactions in integrin signaling.
  Cell Adh Migr, 4, 243-248.  
19530249 D.Langosch, and I.T.Arkin (2009).
Interaction and conformational dynamics of membrane-spanning protein helices.
  Protein Sci, 18, 1343-1358.  
19948488 F.Saltel, E.Mortier, V.P.Hytönen, M.C.Jacquier, P.Zimmermann, V.Vogel, W.Liu, and B.Wehrle-Haller (2009).
New PI(4,5)P2- and membrane proximal integrin-binding motifs in the talin head control beta3-integrin clustering.
  J Cell Biol, 187, 715-731.  
19704023 J.P.Xiong, B.Mahalingham, J.L.Alonso, L.A.Borrelli, X.Rui, S.Anand, B.T.Hyman, T.Rysiok, D.Müller-Pompalla, S.L.Goodman, and M.A.Arnaout (2009).
Crystal structure of the complete integrin alphaVbeta3 ectodomain plus an alpha/beta transmembrane fragment.
  J Cell Biol, 186, 589-600.
PDB code: 3ije
19805198 J.Yang, Y.Q.Ma, R.C.Page, S.Misra, E.F.Plow, and J.Qin (2009).
Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.
  Proc Natl Acad Sci U S A, 106, 17729-17734.
PDB code: 2knc
19716803 M.L.Jones, A.J.Shawe-Taylor, C.M.Williams, and A.W.Poole (2009).
Characterization of a novel focal adhesion kinase inhibitor in human platelets.
  Biochem Biophys Res Commun, 389, 198-203.  
19798053 N.J.Anthis, K.L.Wegener, F.Ye, C.Kim, B.T.Goult, E.D.Lowe, I.Vakonakis, N.Bate, D.R.Critchley, M.H.Ginsberg, and I.D.Campbell (2009).
The structure of an integrin/talin complex reveals the basis of inside-out signal transduction.
  EMBO J, 28, 3623-3632.
PDB code: 3g9w
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.