3CJK

Crystal structure of the adduct HAH1-Cd(II)-MNK1.

Summary for 3CJK

• Entry DOI: 10.2210/pdb3cjk/pdb
• Related: 1FE0 1KVI
• Descriptor: Copper transport protein ATOX1, Copper-transporting ATPase 1, CADMIUM ION, ... (4 entities in total)
• Functional Keywords: hah1; atp7a; atp7b; menkes disease; metal homeostasis, chaperone, copper, copper transport, ion transport, metal-binding, transport, alternative splicing, atp-binding, cytoplasm, disease mutation, endoplasmic reticulum, glycoprotein, golgi apparatus, hydrolase, magnesium, membrane, nucleotide-binding, phosphoprotein, polymorphism, transmembrane, metal transport-hydrolase complex, metal transport/hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein. Isoform 3: Cytoplasm, cytosol (Probable). Isoform 5: Endoplasmic reticulum: Q04656
• Total number of polymer chains: 2
• Total formula weight: 15824.46

Authors

Banci, L.,Bertini, I.,Calderone, V.,Felli, I.,Della-Malva, N.,Pavelkova, A.,Rosato, A. (deposition date: 2008-03-13, release date: 2008-12-30, Last modification date: 2023-08-30)

Primary citation

Banci, L.,Bertini, I.,Calderone, V.,Della-Malva, N.,Felli, I.C.,Neri, S.,Pavelkova, A.,Rosato, A.
Copper(I)-mediated protein-protein interactions result from suboptimal interaction surfaces.
Biochem.J., 422:37-42, 2009

PubMed Abstract: The homoeostasis of metal ions in cells is the result of the contribution of several cellular pathways that involve transient, often weak, protein-protein interactions. Metal transfer typically implies the formation of adducts where the metal itself acts as a bridge between proteins, by co-ordinating residues of both interacting partners. In the present study we address the interaction between the human copper(I)-chaperone HAH1 (human ATX1 homologue) and a metal-binding domain in one of its partners, namely the P-type copper-transporting ATPase, ATP7A (ATPase, Cu+ transporting, alpha polypeptide). The adduct was structurally characterized in solution, in the presence of copper(I), and through X-ray crystallography, upon replacing copper(I) with cadmium(II). Further insight was obtained through molecular modelling techniques and site-directed mutagenesis. It was found that the interaction involves a relatively small interface (less than 1000 A(2), 1 A=0.1 nm) with a low fraction of non-polar atoms. These observations provide a possible explanation for the low affinity of the two apoproteins. It appears that electrostatics is important in selecting which domain of the ATPase is able to form detectable amounts of the metal-mediated adduct with HAH1.

PubMed: 19453293
DOI: 10.1042/BJ20090422

Experimental method

X-RAY DIFFRACTION (1.8 Å)