1XK4

Crystal structure of human calprotectin(S100A8/S100A9)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.160 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins

Korndoerfer, I.P.Brueckner, F.Skerra, A.

(2007) J Mol Biol 370: 887-898

  • DOI: https://doi.org/10.1016/j.jmb.2007.04.065
  • Primary Citation of Related Structures:  
    1XK4

  • PubMed Abstract: 

    The EF-hand proteins S100A8 and S100A9 are important calcium signalling proteins that are involved in wound healing and provide clinically relevant markers of inflammatory processes, such as rheumatoid arthritis and inflammatory bowel disease. Both can form homodimers via distinct modes of association, probably of lesser stability in the case of S100A9, whereas in the presence of calcium S100A8 and S100A9 associate to calprotectin, the physiologically active heterooligomer. Here we describe the crystal structure of the (S100A8/S100A9)(2) heterotetramer at 1.8 A resolution. Its quaternary structure illustrates how specific heteroassociation is energetically driven by a more extensive burial of solvent accessible surface areas in both proteins, most pronounced for S100A9, thus leading to a dimer of heterodimers. A major contribution to tetramer association is made by the canonical calcium binding loops in the C-terminal halves of the two proteins. The mode of heterodimerisation in calprotectin more closely resembles the subunit association previously observed in the S100A8 homodimer and provides trans stabilisation for S100A9, which manifests itself in a significantly elongated C-terminal alpha-helix in the latter. As a consequence, two different putative zinc binding sites emerge at the S100A8/S100A9 subunit interface. One of these corresponds to a high affinity arrangement of three His residues and one Asp side-chain, which is unique to the heterotetramer. This structural feature explains the well known Zn(2+) binding activity of calprotectin, whose overexpression can cause strong dysregulation of zinc homeostasis with severe clinical symptoms.


  • Organizational Affiliation

    Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calgranulin A
A, B, E, F, I
A, B, E, F, I, J
93Homo sapiensMutation(s): 1 
Gene Names: S100A8
UniProt & NIH Common Fund Data Resources
Find proteins for P05109 (Homo sapiens)
Explore P05109 
Go to UniProtKB:  P05109
PHAROS:  P05109
GTEx:  ENSG00000143546 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05109
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Calgranulin B
C, D, G, H, K
C, D, G, H, K, L
113Homo sapiensMutation(s): 1 
Gene Names: S100A9
UniProt & NIH Common Fund Data Resources
Find proteins for P06702 (Homo sapiens)
Explore P06702 
Go to UniProtKB:  P06702
PHAROS:  P06702
GTEx:  ENSG00000163220 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06702
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FLC
Query on FLC

Download Ideal Coordinates CCD File 
BA [auth F]CITRATE ANION
C6 H5 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-K
CA
Query on CA

Download Ideal Coordinates CCD File 
CA [auth G]
DA [auth G]
EA [auth H]
FA [auth H]
GA [auth I]
CA [auth G],
DA [auth G],
EA [auth H],
FA [auth H],
GA [auth I],
HA [auth I],
IA [auth J],
JA [auth J],
LA [auth K],
M [auth A],
MA [auth K],
N [auth A],
NA [auth L],
OA [auth L],
P [auth B],
Q [auth B],
S [auth C],
T [auth C],
U [auth D],
V [auth D],
W [auth E],
X [auth E],
Y [auth F],
Z [auth F]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
AA [auth F],
KA [auth J],
O [auth A],
R [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.160 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.509α = 90
b = 78.697β = 94.94
c = 177.411γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
CCP4data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-10-18
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2015-02-25
    Changes: Database references
  • Version 1.4: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description