1DM5

ANNEXIN XII E105K HOMOHEXAMER CRYSTAL STRUCTURE

Summary for 1DM5

• Entry DOI: 10.2210/pdb1dm5/pdb
• Related: 1AEI
• Descriptor: ANNEXIN XII E105K MUTANT HOMOHEXAMER, CALCIUM ION (3 entities in total)
• Functional Keywords: homohexamer, novel ph-dependent hexamerization switch e76, low calcium form, mixed typeii/typeiii calcium binding site, e105k epsilon amino group replaces intermolecular calcium, unknown function
• Biological source: Hydra vulgaris
• Total number of polymer chains: 6
• Total formula weight: 210588.09

Authors

Cartailler, J.P.,Haigler, H.T.,Luecke, H. (deposition date: 1999-12-13, release date: 2000-03-20, Last modification date: 2024-02-07)

Primary citation

Cartailler, J.P.,Haigler, H.T.,Luecke, H.
Annexin XII E105K crystal structure: identification of a pH-dependent switch for mutant hexamerization.
Biochemistry, 39:2475-2483, 2000

PubMed Abstract: Annexins are a family of calcium- and phospholipid-binding proteins involved with numerous cellular processes including membrane fusion, ion channel activity, and heterocomplex formation with other proteins. The annexin XII (ANXB12) crystal structure presented evidence that calcium mediates the formation of a hexamer through a novel intermolecular calcium-binding site [Luecke et al. (1995) Nature 378, 512-515]. In an attempt to disrupt hexamerization, we mutated a conserved key ligand in the intermolecular calcium-binding site, Glu105, to lysine. Despite its occurrence in a new spacegroup, the 1.93 A resolution structure reveals a hexamer with the Lys105 epsilon-amino group nearly superimposable with the original intermolecular calcium position. Our analysis shows that the mutation is directly involved in stabilizing the hexamer. The local residues are reoriented to retain affinity between the two trimers via a pH-dependent switch residue, Glu76, which is now protonated, allowing it to form tandem hydrogen bonds with the backbone carbonyl and nitrogen atoms of Thr103 located across the trimer interface. The loss of the intermolecular calcium-binding site is recuperated by extensive hydrogen bonding favoring hexamer stabilization. The presence of this mutant structure provides further evidence for hexameric annexin XII, and possible in vivo roles are discussed.

PubMed: 10704197
DOI: 10.1021/bi992278d

Experimental method

X-RAY DIFFRACTION (1.93 Å)