PDBsum entry 1p1z

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Immune system PDB id
Protein chains
255 a.a. *
97 a.a. *
118 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system
Title: X-ray crystal structure of the lectin-like natural killer cell receptor ly-49c bound to its mhc class i ligand h-2kb
Structure: H-2 class i histocompatibility antigen, k-b alpha chain. Chain: a. Synonym: h-2kb. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. Ovalbumin peptide.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: h2-k. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Other_details: the peptide was chemically synthesized. The
Biol. unit: Tetramer (from PDB file)
3.26Å     R-factor:   0.263     R-free:   0.316
Authors: N.Dimasi,K.Natarajan,G.Rangjin,J.Dam,D.H.Margulies, R.A.Mariuzza
Key ref:
J.Dam et al. (2003). Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b). Nat Immunol, 4, 1213-1222. PubMed id: 14595439 DOI: 10.1038/ni1006
14-Apr-03     Release date:   11-Nov-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01901  (HA1B_MOUSE) -  H-2 class I histocompatibility antigen, K-B alpha chain
369 a.a.
255 a.a.
Protein chain
Pfam   ArchSchema ?
P01887  (B2MG_MOUSE) -  Beta-2-microglobulin
119 a.a.
97 a.a.*
Protein chain
Pfam   ArchSchema ?
Q64329  (KLRA3_MOUSE) -  Killer cell lectin-like receptor 3
266 a.a.
118 a.a.*
Key:    PfamA 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     extracellular region   10 terms 
  Biological process     immune system process   13 terms 
  Biochemical function     protein binding     4 terms  


DOI no: 10.1038/ni1006 Nat Immunol 4:1213-1222 (2003)
PubMed id: 14595439  
Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b).
J.Dam, R.Guan, K.Natarajan, N.Dimasi, L.K.Chlewicki, D.M.Kranz, P.Schuck, D.H.Margulies, R.A.Mariuzza.
The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes.
  Selected figure(s)  
Figure 2.
Figure 2. Structure of Ly49/MHC class I complexes. (a) Superposition of wild-type (blue) and mutant (red) Ly49C -H-2Kb complexes in the crystallographic asymmetric unit, indicating close overall similarity. (b) Electron density in the interface of the mutant Ly49C -H-2Kb complex. The F[o] - F[c] omit map at 2.9 resolution is contoured at 2.5 . Ly49C residues 239 -243 (red), H-2Kb heavy chain residues 111 -117 (blue) and [2]M residues 58 -60 (yellow) were excluded from the map calculation. (c) Ribbon diagram of the mutant Ly49C -H-2Kb complex, in which the crystallographic Ly49C dimer (red) crosslinks two MHC class I molecules. (d) Structure of the Ly49A -H-2D^d complex, showing the asymmetric interaction between the Ly49A dimer (green) and two MHC class I molecules. The two interaction surfaces, site 1 and site 2, are indicated by the dashed circle and rectangle, respectively. In c and d, the H-2Kb heavy chain is blue, the ovalbumin peptide (ball-and-stick representation) is red and [2]M is yellow.
Figure 6.
Figure 6. Comparison of hydrogen-bonding networks at the Ly49C -H-2Kb and Ly49A -H-2D^d interfaces. (a) Detailed view (stereo diagram) of the Ly49C -H-2Kb interface showing hydrogen bonds (dotted black lines) between Ly49C (red) and the H-2Kb heavy chain (blue) or [2]M (violet); the side chains of interacting residues are yellow. The portion of the Ly49C L3 loop, encompassing residues 226 -231, which is disordered in both mutant and wild-type structures, is drawn arbitrarily (red balls). With the exception of H-2Kb residues Asp212 and Thr214, whose side chains could potentially interact with the disordered L3 loop of Ly49C, only residues forming hydrogen bonds are shown. (b) Stereo diagram showing hydrogen bonds between Ly49A (green) and the H-2D^d heavy chain (blue) or [2]M (violet) at the site 2 interface of the Ly49A -H-2D^d complex.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2003, 4, 1213-1222) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20567250 H.J.Pegram, D.M.Andrews, M.J.Smyth, P.K.Darcy, and M.H.Kershaw (2011).
Activating and inhibitory receptors of natural killer cells.
  Immunol Cell Biol, 89, 216-224.  
19549850 D.Ito, Y.M.Iizuka, M.P.Katepalli, and K.Iizuka (2009).
Essential role of the Ly49A stalk region for immunological synapse formation and signaling.
  Proc Natl Acad Sci U S A, 106, 11264-11269.  
19265140 J.A.Hammond, L.A.Guethlein, L.Abi-Rached, A.K.Moesta, and P.Parham (2009).
Evolution and survival of marine carnivores did not require a diversity of killer cell Ig-like receptors or Ly49 NK cell receptors.
  J Immunol, 182, 3618-3627.  
19818651 J.Back, E.L.Malchiodi, S.Cho, L.Scarpellino, P.Schneider, M.C.Kerzic, R.A.Mariuzza, and W.Held (2009).
Distinct conformations of Ly49 natural killer cell receptors mediate MHC class I recognition in trans and cis.
  Immunity, 31, 598-608.
PDB codes: 3g8k 3g8l
19251634 M.Inui, Y.Kikuchi, N.Aoki, S.Endo, T.Maeda, A.Sugahara-Tobinai, S.Fujimura, A.Nakamura, A.Kumanogoh, M.Colonna, and T.Takai (2009).
Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12.
  Proc Natl Acad Sci U S A, 106, 4816-4821.  
19604491 Y.Li, M.Hofmann, Q.Wang, L.Teng, L.K.Chlewicki, H.Pircher, and R.A.Mariuzza (2009).
Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.
  Immunity, 31, 35-46.
PDB codes: 3ff7 3ff8 3ff9
  18566392 A.H.Davis, N.V.Guseva, B.L.Ball, and J.W.Heusel (2008).
Characterization of murine cytomegalovirus m157 from infected cells and identification of critical residues mediating recognition by the NK cell receptor Ly49H.
  J Immunol, 181, 265-275.  
18201367 D.J.Gibbings, A.F.Ghetu, R.Dery, and A.D.Befus (2008).
Macrophage migration inhibitory factor has a MHC class I-like motif and function.
  Scand J Immunol, 67, 121-132.  
18597489 E.Hooley, E.Papagrigoriou, A.Navdaev, A.V.Pandey, J.M.Clemetson, K.J.Clemetson, and J.Emsley (2008).
The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure.
  Biochemistry, 47, 7831-7837.
PDB code: 3bx4
18426793 L.Deng, S.Cho, E.L.Malchiodi, M.C.Kerzic, J.Dam, and R.A.Mariuzza (2008).
Molecular architecture of the major histocompatibility complex class I-binding site of Ly49 natural killer cell receptors.
  J Biol Chem, 283, 16840-16849.
PDB codes: 3c8j 3c8k 3cad
18336206 L.R.Pepper, Y.K.Cho, E.T.Boder, and E.V.Shusta (2008).
A decade of yeast surface display technology: where are we now?
  Comb Chem High Throughput Screen, 11, 127-134.  
18948016 M.Pyzik, A.Kielczewska, and S.M.Vidal (2008).
NK cell receptors and their MHC class I ligands in host response to cytomegalovirus: insights from the mouse genome.
  Semin Immunol, 20, 331-342.  
18574582 S.L.Rogers, and J.Kaufman (2008).
High allelic polymorphism, moderate sequence diversity and diversifying selection for B-NK but not B-lec, the pair of lectin-like receptor genes in the chicken MHC.
  Immunogenetics, 60, 461-475.  
18309314 W.Held, and R.A.Mariuzza (2008).
Cis interactions of immunoreceptors with MHC and non-MHC ligands.
  Nat Rev Immunol, 8, 269-278.  
17132623 A.A.Watson, J.Brown, K.Harlos, J.A.Eble, T.S.Walter, and C.A.O'Callaghan (2007).
The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2.
  J Biol Chem, 282, 3165-3172.
PDB code: 2c6u
17950006 C.A.Velikovsky, L.Deng, L.K.Chlewicki, M.M.Fernández, V.Kumar, and R.A.Mariuzza (2007).
Structure of natural killer receptor 2B4 bound to CD48 reveals basis for heterophilic recognition in signaling lymphocyte activation molecule family.
  Immunity, 27, 572-584.
PDB codes: 2ptt 2ptu 2ptv
17537914 E.J.Adams, Z.S.Juo, R.T.Venook, M.J.Boulanger, H.Arase, L.L.Lanier, and K.C.Garcia (2007).
Structural elucidation of the m157 mouse cytomegalovirus ligand for Ly49 natural killer cell receptors.
  Proc Natl Acad Sci U S A, 104, 10128-10133.
PDB code: 2nyk
17360463 J.Back, A.Chalifour, L.Scarpellino, and W.Held (2007).
Stable masking by H-2Dd cis ligand limits Ly49A relocalization to the site of NK cell/target cell contact.
  Proc Natl Acad Sci U S A, 104, 3978-3983.  
17853390 K.Daly, W.B.Church, K.Nicholas, and P.Williamson (2007).
Comparative modeling of marsupial MHC class I molecules identifies structural polymorphisms affecting functional motifs.
  J Exp Zool Part A Ecol Genet Physiol, 307, 611-624.  
17334368 L.Deng, R.J.Langley, P.H.Brown, G.Xu, L.Teng, Q.Wang, M.I.Gonzales, G.G.Callender, M.I.Nishimura, S.L.Topalian, and R.A.Mariuzza (2007).
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor.
  Nat Immunol, 8, 398-408.
PDB codes: 2ial 2iam 2ian
16500675 K.Natarajan, A.Hicks, J.Mans, H.Robinson, R.Guan, R.A.Mariuzza, and D.H.Margulies (2006).
Crystal structure of the murine cytomegalovirus MHC-I homolog m144.
  J Mol Biol, 358, 157-171.
PDB code: 1u58
16737824 L.Deng, and R.A.Mariuzza (2006).
Structural basis for recognition of MHC and MHC-like ligands by natural killer cell receptors.
  Semin Immunol, 18, 159-166.  
16737823 S.Malarkannan (2006).
The balancing act: inhibitory Ly49 regulate NKG2D-mediated NK cell functions.
  Semin Immunol, 18, 186-192.  
16336259 A.N.Zelensky, and J.E.Gready (2005).
The C-type lectin-like domain superfamily.
  FEBS J, 272, 6179-6217.  
15863475 J.Dam, C.A.Velikovsky, R.A.Mariuzza, C.Urbanke, and P.Schuck (2005).
Sedimentation velocity analysis of heterogeneous protein-protein interactions: Lamm equation modeling and sedimentation coefficient distributions c(s).
  Biophys J, 89, 619-634.  
15863474 J.Dam, and P.Schuck (2005).
Sedimentation velocity analysis of heterogeneous protein-protein interactions: sedimentation coefficient distributions c(s) and asymptotic boundary profiles from Gilbert-Jenkins theory.
  Biophys J, 89, 651-666.  
16132082 J.Kelley, L.Walter, and J.Trowsdale (2005).
Comparative genomics of natural killer cell receptor gene clusters.
  PLoS Genet, 1, 129-139.  
15771571 L.L.Lanier (2005).
NK cell recognition.
  Annu Rev Immunol, 23, 225-274.  
15895081 M.P.Desrosiers, A.Kielczewska, J.C.Loredo-Osti, S.G.Adam, A.P.Makrigiannis, S.Lemieux, T.Pham, M.B.Lodoen, K.Morgan, L.L.Lanier, and S.M.Vidal (2005).
Epistasis between mouse Klra and major histocompatibility complex class I loci is associated with a new mechanism of natural killer cell-mediated innate resistance to cytomegalovirus infection.
  Nat Genet, 37, 593-599.  
15661035 N.Dimasi, and R.Biassoni (2005).
Structural and functional aspects of the Ly49 natural killer cell receptors.
  Immunol Cell Biol, 83, 1-8.  
20476991 R.Biassoni, and N.Dimasi (2005).
Human natural killer cell receptor functions and their implication in diseases.
  Expert Rev Clin Immunol, 1, 405-417.  
15549676 R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2003 commercial optical biosensor literature.
  J Mol Recognit, 18, 1.  
15084288 A.K.Mitra, H.Célia, G.Ren, J.G.Luz, I.A.Wilson, and L.Teyton (2004).
Supine orientation of a murine MHC class I molecule on the membrane bilayer.
  Curr Biol, 14, 718-724.  
15493870 C.A.Wright, P.Kozik, M.Zacharias, and S.Springer (2004).
Tapasin and other chaperones: models of the MHC class I loading complex.
  Biol Chem, 385, 763-778.  
15134782 P.J.Leibson (2004).
The regulation of lymphocyte activation by inhibitory receptors.
  Curr Opin Immunol, 16, 328-336.  
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.