4GGF

Crystal structure of Mn2+ bound calprotectin

Summary for 4GGF

• Entry DOI: 10.2210/pdb4ggf/pdb
• Descriptor: Protein S100-A8, Protein S100-A9, CALCIUM ION, ... (7 entities in total)
• Functional Keywords: s100, ef-hand, antimicrobial protein
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P05109 P06702
• Total number of polymer chains: 8
• Total formula weight: 98047.93

Authors

Damo, S.M.,Fritz, G. (deposition date: 2012-08-06, release date: 2013-02-20, Last modification date: 2023-09-13)

Primary citation

Damo, S.M.,Kehl-Fie, T.E.,Sugitani, N.,Holt, M.E.,Rathi, S.,Murphy, W.J.,Zhang, Y.,Betz, C.,Hench, L.,Fritz, G.,Skaar, E.P.,Chazin, W.J.
Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.
Proc.Natl.Acad.Sci.USA, 110:3841-3846, 2013

PubMed Abstract: The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn(2+) sequestration. The asymmetry of the CP heterodimer creates a single Mn(2+)-binding site from six histidine residues, which distinguishes CP from all other Mn(2+)-binding proteins. Analysis of CP mutants with altered metal-binding properties revealed that, despite both Mn(2+) and Zn(2+) being essential metals, maximal growth inhibition of multiple bacterial pathogens requires Mn(2+) sequestration. These data establish the importance of Mn(2+) sequestration in defense against infection, explain the broad-spectrum antimicrobial activity of CP relative to other S100 proteins, and clarify the impact of metal depletion on the innate immune response to infection.

PubMed: 23431180
DOI: 10.1073/pnas.1220341110

Experimental method

X-RAY DIFFRACTION (1.6 Å)