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PDBsum entry 1mhp
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protein metals Protein-protein interface(s) links
Immune system PDB id
1mhp

 

 

 

 

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Contents
Protein chains
184 a.a. *
219 a.a. *
212 a.a. *
118 a.a. *
105 a.a. *
Metals
_MN ×2
* Residue conservation analysis
PDB id:
1mhp
Name: Immune system
Title: Crystal structure of a chimeric alpha1 integrin i-domain in complex with the fab fragment of a humanized neutralizing antibody
Structure: Integrin alpha 1, (residues 169-360). Chain: a, b. Fragment: alpha1 i-domain. Synonym: laminin and collagen receptor, vla-1, cd49a. Engineered: yes. Mutation: yes. Fab fragment, heavy chain. Chain: h, x. Engineered: yes.
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: cricetulus griseus.
Biol. unit: Hexamer (from PQS)
Resolution:
2.80Å     R-factor:   0.222     R-free:   0.272
Authors: M.Karpusas,F.Taylor,J.Ferrant,P.Weinreb,E.Garber
Key ref:
M.Karpusas et al. (2003). Crystal structure of the alpha1beta1 integrin I domain in complex with an antibody Fab fragment. J Mol Biol, 327, 1031-1041. PubMed id: 12662928 DOI: 10.1016/S0022-2836(03)00203-1
Date:
20-Aug-02     Release date:   15-Apr-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P18614  (ITA1_RAT) -  Integrin alpha-1 from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1180 a.a.
184 a.a.*
Protein chain
No UniProt id for this chain
Struc: 219 a.a.
Protein chain
No UniProt id for this chain
Struc: 212 a.a.
Protein chain
No UniProt id for this chain
Struc: 118 a.a.
Protein chain
No UniProt id for this chain
Struc: 105 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 

 
DOI no: 10.1016/S0022-2836(03)00203-1 J Mol Biol 327:1031-1041 (2003)
PubMed id: 12662928  
 
 
Crystal structure of the alpha1beta1 integrin I domain in complex with an antibody Fab fragment.
M.Karpusas, J.Ferrant, P.H.Weinreb, A.Carmillo, F.R.Taylor, E.A.Garber.
 
  ABSTRACT  
 
The alpha1beta1 (VLA-1) integrin is a cell-surface receptor for collagen and laminin and has been implicated in biological pathways involved in several pathological processes. These processes may be inhibited by the monoclonal antibody AQC2, which binds with high affinity to human alpha1beta1 integrin. To understand the structural basis of the inhibition we determined the crystal structure of the complex of a chimeric rat/human I domain of the alpha1beta1 integrin and the Fab fragment of humanized AQC2 antibody. The structure of the complex shows that the antibody blocks the collagen binding site of the I domain. An aspartate residue, from the CDR3 loop of the antibody heavy chain, coordinates the MIDAS metal ion in a manner similar to that of a glutamate residue from collagen. Substitution of the aspartate residue by alanine or arginine results in significant reduction of antibody binding affinity. Interestingly, although the mode of metal ion coordination resembles that of the open conformation, the I domain maintains an overall closed conformation previously observed only for unliganded I domains.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Stereo diagram of a simulated annealing omit map in the vicinity of the MIDAS site. The map was contoured at 1.0s. The Figure was prepared with QUANTA. 		Figure 4.
Figure 4. Comparison of I domain structures. (a) Stereo diagram of superimposed complexed and uncomplexed a1b1 I domains. The yellow ribbon corresponds to the a1 I domain-Fab complex and the blue ribbon to the uncomplexed rat I domain (PDB entry 1aly). (b) Superimposition of the MIDAS motifs from the a1 I domain-Fab (in green color) and a2 I domain-collagen (in gray color) complex structures. (c) Superimposition of the MIDAS motifs from the a1 I domain-Fab (in green color) and uncomplexed a2 I domain (in gray color) structures. Labels correspond to the a1 I domain.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 327, 1031-1041) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21360611 M.H.Niemi, K.Takkinen, L.K.Amundsen, H.Söderlund, J.Rouvinen, and M.Höyhtyä (2011).
The testosterone binding mechanism of an antibody derived from a naïve human scFv library.
  J Mol Recognit, 24, 209-219.
PDB code: 3kdm
19805116 H.Zhang, J.H.Liu, W.Yang, T.Springer, M.Shimaoka, and J.H.Wang (2009).
Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1.
  Proc Natl Acad Sci U S A, 106, 18345-18350.
PDB codes: 3hi5 3hi6
19074157 L.A.Clark, P.A.Boriack-Sjodin, E.Day, J.Eldredge, C.Fitch, M.Jarpe, S.Miller, Y.Li, K.Simon, and H.W.van Vlijmen (2009).
An antibody loop replacement design feasibility study and a loop-swapped dimer structure.
  Protein Eng Des Sel, 22, 93.
PDB code: 3eot
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
16597831 L.A.Clark, P.A.Boriack-Sjodin, J.Eldredge, C.Fitch, B.Friedman, K.J.Hanf, M.Jarpe, S.F.Liparoto, Y.Li, A.Lugovskoy, S.Miller, M.Rushe, W.Sherman, K.Simon, and H.Van Vlijmen (2006).
Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design.
  Protein Sci, 15, 949-960.
PDB code: 2b2x
16963559 M.Shimaoka, M.Kim, E.H.Cohen, W.Yang, N.Astrof, D.Peer, A.Salas, A.Ferrand, and T.A.Springer (2006).
AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes.
  Proc Natl Acad Sci U S A, 103, 13991-13996.  
16212500 M.A.Arnaout, B.Mahalingam, and J.P.Xiong (2005).
Integrin structure, allostery, and bidirectional signaling.
  Annu Rev Cell Dev Biol, 21, 381-410.  
15986132 S.Kuphal, R.Bauer, and A.K.Bosserhoff (2005).
Integrin signaling in malignant melanoma.
  Cancer Metastasis Rev, 24, 195-222.  
15070893 K.Ajroud, T.Sugimori, W.H.Goldmann, D.M.Fathallah, J.P.Xiong, and M.A.Arnaout (2004).
Binding Affinity of Metal Ions to the CD11b A-domain Is Regulated by Integrin Activation and Ligands.
  J Biol Chem, 279, 25483-25488.  
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.  
14660600 Y.Nymalm, J.S.Puranen, T.K.Nyholm, J.Käpylä, H.Kidron, O.T.Pentikäinen, T.T.Airenne, J.Heino, J.P.Slotte, M.S.Johnson, and T.A.Salminen (2004).
Jararhagin-derived RKKH peptides induce structural changes in alpha1I domain of human integrin alpha1beta1.
  J Biol Chem, 279, 7962-7970.
PDB codes: 1pt6 1qcy
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.

 

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