PDBsum entry 2wcf

Metal binding protein

PDB id: 2wcf

Contents

Protein chain

(+ 0 more) 91 a.a. *

Metals

_NA ×2

Waters ×20

* Residue conservation analysis

PDB id:

2wcf

Name:

Metal binding protein

Title:

Calcium-free (apo) s100a12

Structure:

Protein s100-a12. Chain: a, b, c, d, e, f. Fragment: residues 2-92. Synonym: s100 calcium-binding protein a12, calgranulin-c, cgrp, neutrophil s100 protein, calcium-binding protein in amniotic fluid 1, p6, cagc, caaf1, s100a12, calcitermin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.78Å R-factor: 0.248 R-free: 0.323

Authors:

O.V.Moroz,E.V.Blagova,A.J.Wilkinson,K.S.Wilson,I.B.Bronstein

Key ref:

O.V.Moroz et al. (2009). The crystal structures of human S100A12 in apo form and in complex with zinc: new insights into S100A12 oligomerisation. J Mol Biol, 391, 536-551. PubMed id: 19501594 DOI: 10.1016/j.jmb.2009.06.004

Date:

11-Mar-09 Release date: 23-Jun-09

Protein chains

P80511  (S10AC_HUMAN) -  Protein S100-A12 from Homo sapiens

Seq: 92 a.a.

Struc: 91 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.jmb.2009.06.004

J Mol Biol 391:536-551 (2009)

PubMed id: 19501594

The crystal structures of human S100A12 in apo form and in complex with zinc: new insights into S100A12 oligomerisation.

O.V.Moroz, E.V.Blagova, A.J.Wilkinson, K.S.Wilson, I.B.Bronstein.

ABSTRACT

The functions of the members of the S100 family of EF-hand proteins are modulated by calcium and, in a number of cases, by zinc or copper. One such protein is S100A12, which is implicated in inflammation and host-parasite responses. Previously, we reported the structures of human S100A12 in both low (dimeric) and high (hexameric) calcium forms and, in addition, that of a complex with copper and calcium. Here we report the crystal structures of the metal-free apo form of human S100A12 at 1.77 A resolution and of the zinc complex in two crystal forms (P2(1)2(1)2(1) and F222) to 1.88 A and 1.73 A resolution, respectively. These are the first structures of a zinc-only complex of an S100 protein to be determined. The zinc complex structure shows significant differences from those of both calcium-loaded and apo-S100A12 structures, and comparisons suggest an explanation for the zinc-induced 1500-fold increase in calcium affinity. In addition, the new structures provide insight into the role of zinc-calcium interplay in the transition of S100A12 from a dimer through a tetramer to a hexamer. The role of both zinc and calcium in target binding by S100A12 during host-parasite responses is confirmed by experiments with paramyosin from the tropical parasites Onchocerca volvulus and Brugia malayi.

Selected figure(s)

Figure 1.
Fig. 1. Comparison of apo and metal complex structures. (a) Stereoview of the Ca/Cu-S100A12 dimer in ribbon representation, with individual subunits shown in red and blue. The chain topology, subunit arrangement, and juxtaposition of metal-binding sites are typical of metal-bound S100 proteins. Calcium ions bound to EF-1 and EF-2 are shown in yellow, with the two copper ions at the subunit interface shown in brown. (b) Superposed structures of subunits of apo-S100A12 (green), apo-S100A2 (PDB code 1RGI; magenta), apo-S100A3 (PDB code 1kso; yellow), and apo-S100A6 (PDB code 1k9p; red). The distinct conformation of the C-terminus in S100A12 is apparent. (c) Ribbon representation of the superimposed dimers of apo-S100A12 (green), Zn-S100A12 (blue), and Ca/Cu-S100A12 (red; PDB code 1odb). The α-helical elements of subunits in the dimer are labelled and distinguished by an apostrophe. The figure illustrates changes in the dimerisation interface between the apo structure and the metal-bound structure, as well as changes in the position of helix HIII and the hinge region. The figure was generated using CCP4mg,^21 as were as all other structure figures.

Figure 5.
Fig. 5. The S100A12 zinc-binding site. (a) Superposition of the zinc-binding site of Zn-S100A12 (residues from both subunits of the dimer contribute to zinc binding; one subunit is shown in cyan and another is shown in green) on the same site of Ca/Cu-S100A12 (PDB code 1odb; all shown in yellow). The zinc ion is shown in cyan, and copper is shown in brown. (b) Superposition of the zinc-binding sites of Zn-S100A12 (cyan), S100A7 (PDB code 3psr; light green), and S100B (PDB code 3cr2; magenta). Zinc ions are shown in corresponding colors.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 391, 536-551) copyright 2009.

Figures were selected by an automated process.