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Immune system PDB id
1dgq
Jmol
Contents
Protein chain
188 a.a. *
* Residue conservation analysis
PDB id:
1dgq
Name: Immune system
Title: Nmr solution structure of the inserted domain of human leukocyte function associated antigen-1
Structure: Leukocyte function associated antigen-1. Chain: a. Fragment: inserted domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 22 models
Authors: G.B.Legge,R.W.Kriwacki,J.Chung,U.Hommel,P.Ramage,D.A.Case, H.J.Dyson,P.E.Wright
Key ref:
G.B.Legge et al. (2000). NMR solution structure of the inserted domain of human leukocyte function associated antigen-1. J Mol Biol, 295, 1251-1264. PubMed id: 10653701 DOI: 10.1006/jmbi.1999.3409
Date:
24-Nov-99     Release date:   03-Feb-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P20701  (ITAL_HUMAN) -  Integrin alpha-L
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1170 a.a.
188 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 

 
DOI no: 10.1006/jmbi.1999.3409 J Mol Biol 295:1251-1264 (2000)
PubMed id: 10653701  
 
 
NMR solution structure of the inserted domain of human leukocyte function associated antigen-1.
G.B.Legge, R.W.Kriwacki, J.Chung, U.Hommel, P.Ramage, D.A.Case, H.J.Dyson, P.E.Wright.
 
  ABSTRACT  
 
The interaction between the leukocyte function-associated antigen-1 (LFA-1) and the intercellular adhesion molecule is thought to be mediated primarily via the inserted domain (I-domain) in the alpha-subunit. The activation of LFA-1 is an early step in triggering the adhesion of leukocytes to target cells decorated with intercellular adhesion molecules. There is some disagreement in the literature over the respective roles of conformational changes in the I-domain and of divalent cations (Mg(2+), Mn(2+)) in the activation of LFA-1 for intercellular adhesion molecule binding. X-ray crystallographic structures of the I-domains of LFA-1 and Mac-1 in the presence and absence of cations show structural differences in the C-terminal alpha-helix; this change was proposed to represent the active and inactive conformations of the I-domain. However, more recent X-ray results have called this proposal into question. The solution structure of the Mg(2+) complex of the I-domain of LFA-1 has been determined by NMR methods, using a model-based approach to nuclear Overhauser enhancement spectroscopy peak assignment. The protein adopts the same structure in solution as that of the published I-domain X-ray structures, but the C-terminal region, where the X-ray structures are most different from each other, is different again in the solution structures. The secondary structure of this helix is well formed, but NMR relaxation data indicate that there is considerable flexibility present, probably consisting of breathing or segmental motion of the helix. The conformational diversity seen in the various X-ray structures could be explained as a result of the inherent flexibility of this C-terminal region and as a result of crystal contacts. Our NMR data are consistent with a model where the C-terminal helix has the potential flexibility to take up alternative conformations, for example, in the presence and absence of the intercellular adhesion molecule ligand. The role of divalent cations appears from our results not to be as a direct mediator of a conformational change that alters affinity for the ligand. Rather, the presence of the cation appears to be involved in some other way in ligand binding, perhaps by acting as a bridge to the ligand and by modulation of the charge of the binding surface.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Ribbon diagram of the mean NMR structure showing helices (red/yellow), b-sheets (blue) and loops (gray). The structure is rotated by 90 ° between views (a) and (b) in order to highlight the (a) b-sheet and the (b) a-helices. The location of the metal ion is not shown, but it would be in the top right of the molecule in A. The Figure was prepared with the program MOLMOL (Koradi et al., 1996). 		Figure 9.
Figure 9. Stereo superposition of the side-chains of residues Asp137, Ser139, Thr141, Thr206, and Asp239 for the 22 NMR structures of the Mg 2+ -LFA-1 I-domain. These residues form the metal binding site in the X-ray crystal structure of the Mn 2+ complex of the LFA-1 I- domain (Qu & Leahy, 1995). Figure prepared with the program MOLMOL (Koradi et al., 1996).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 295, 1251-1264) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19258452 S.Li, H.Wang, B.Peng, M.Zhang, D.Zhang, S.Hou, Y.Guo, and J.Ding (2009).
Efalizumab binding to the LFA-1 alphaL I domain blocks ICAM-1 binding via steric hindrance.
  Proc Natl Acad Sci U S A, 106, 4349-4354.
PDB codes: 3eo9 3eoa 3eob
18417478 L.J.Lambert, A.A.Bobkov, J.W.Smith, and F.M.Marassi (2008).
Competitive interactions of collagen and a jararhagin-derived disintegrin peptide with the integrin alpha2-I domain.
  J Biol Chem, 283, 16665-16672.  
18199751 R.Carreño, D.Li, M.Sen, I.Nira, T.Yamakawa, Q.Ma, and G.B.Legge (2008).
A mechanism for antibody-mediated outside-in activation of LFA-1.
  J Biol Chem, 283, 10642-10648.  
18020948 K.Hänel, and D.Willbold (2007).
SARS-CoV accessory protein 7a directly interacts with human LFA-1.
  Biol Chem, 388, 1325-1332.  
17523188 M.Sen, and G.B.Legge (2007).
Pactolus I-domain: functional switching of the Rossmann fold.
  Proteins, 68, 626-635.
PDB code: 2iue
17868072 T.Zimmerman, J.Oyarzabal, E.S.Sebastián, S.Majumdar, B.A.Tejo, T.J.Siahaan, and F.J.Blanco (2007).
ICAM-1 peptide inhibitors of T-cell adhesion bind to the allosteric site of LFA-1. An NMR characterization.
  Chem Biol Drug Des, 70, 347-353.  
16100282 A.O.Eniola, E.F.Krasik, L.A.Smith, G.Song, and D.A.Hammer (2005).
I-domain of lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow.
  Biophys J, 89, 3577-3588.  
16234238 F.Zhang, W.D.Marcus, N.H.Goyal, P.Selvaraj, T.A.Springer, and C.Zhu (2005).
Two-dimensional kinetics regulation of alphaLbeta2-ICAM-1 interaction by conformational changes of the alphaL-inserted domain.
  J Biol Chem, 280, 42207-42218.  
15576028 M.Jin, I.Andricioaei, and T.A.Springer (2004).
Conversion between three conformational states of integrin I domains with a C-terminal pull spring studied with molecular dynamics.
  Structure, 12, 2137-2147.  
15060526 M.R.Arkin, and J.A.Wells (2004).
Small-molecule inhibitors of protein-protein interactions: progressing towards the dream.
  Nat Rev Drug Discov, 3, 301-317.  
12682007 J.J.Wilson, O.Matsushita, A.Okabe, and J.Sakon (2003).
A bacterial collagen-binding domain with novel calcium-binding motif controls domain orientation.
  EMBO J, 22, 1743-1752.
PDB codes: 1nqd 1nqj
12526797 M.Shimaoka, T.Xiao, J.H.Liu, Y.Yang, Y.Dong, C.D.Jun, A.McCormack, R.Zhang, A.Joachimiak, J.Takagi, J.H.Wang, and T.A.Springer (2003).
Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation.
  Cell, 112, 99.
PDB codes: 1mjn 1mq8 1mq9 1mqa
  12821302 T.R.Gadek, and R.S.McDowell (2003).
Discovery of small molecule leads in a biotechnology datastream.
  Drug Discov Today, 8, 545-550.  
12554829 T.Vorup-Jensen, C.Ostermeier, M.Shimaoka, U.Hommel, and T.A.Springer (2003).
Structure and allosteric regulation of the alpha X beta 2 integrin I domain.
  Proc Natl Acad Sci U S A, 100, 1873-1878.
PDB code: 1n3y
12368274 A.Salas, M.Shimaoka, S.Chen, C.V.Carman, and T.Springer (2002).
Transition from rolling to firm adhesion is regulated by the conformation of the I domain of the integrin lymphocyte function-associated antigen-1.
  J Biol Chem, 277, 50255-50262.  
12112684 G.B.Legge, G.M.Morris, M.F.Sanner, Y.Takada, A.J.Olson, and F.Grynszpan (2002).
Model of the alphaLbeta2 integrin I-domain/ICAM-1 DI interface suggests that subtle changes in loop orientation determine ligand specificity.
  Proteins, 48, 151-160.
PDB code: 1ij4
12234369 J.Takagi, and T.A.Springer (2002).
Integrin activation and structural rearrangement.
  Immunol Rev, 186, 141-163.  
12234368 M.A.Arnaout (2002).
Integrin structure: new twists and turns in dynamic cell adhesion.
  Immunol Rev, 186, 125-140.  
11988479 M.Shimaoka, J.Takagi, and T.A.Springer (2002).
Conformational regulation of integrin structure and function.
  Annu Rev Biophys Biomol Struct, 31, 485-516.  
11792712 Q.Ma, M.Shimaoka, C.Lu, H.Jing, C.V.Carman, and T.A.Springer (2002).
Activation-induced conformational changes in the I domain region of lymphocyte function-associated antigen 1.
  J Biol Chem, 277, 10638-10641.  
12213832 R.C.Liddington, and M.H.Ginsberg (2002).
Integrin activation takes shape.
  J Cell Biol, 158, 833-839.  
11353828 M.Shimaoka, C.Lu, R.T.Palframan, U.H.von Andrian, A.McCormack, J.Takagi, and T.A.Springer (2001).
Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo.
  Proc Natl Acad Sci U S A, 98, 6009-6014.  
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 codes are shown on the right.