The Cupredoxin-like Domains in Hemocyanins

Institut für Molekulare Biophysik, Johannes Gutenberg-Universität, Jakob Welder Weg 26, 55128 Mainz, Germany.
Biochemical Journal (Impact Factor: 4.4). 12/2009; 426(3):373-8. DOI: 10.1042/BJ20091501
Source: PubMed


Haemocyanins are multimeric oxygen transport proteins, which bind oxygen to type 3 copper sites. Arthropod haemocyanins contain 75-kDa subunits, whereas molluscan haemocyanins contain 350-400-kDa subunits comprising seven or eight different 50 kDa FUs (functional units) designated FU-a to FU-h, each with an active site. FU-h possesses a tail of 100 amino acids not present in the other FUs. In the present study we show by X-ray crystallography that in FU-h of KLH1 (keyhole-limpet-haemocyanin isoform 1) the structure of the tail domain is cupredoxin-like but contains no copper. The copper-free domain 3 in arthropod haemocyanin subunits has also recently been reinterpreted as being cupredoxin-like. We propose that the cupredoxin-like domain in both haemocyanin types once served to upload copper to the active site of the oxygen-binding domain.

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    • "Arthropod hemocyanin consists of three different domains (a N-terminal domain shielding the entrance of the active site, a central domain containing the active site and a immunoglobulin-like C-terminal domain). This significant structural difference might be a reason for the absence of the thioether bond in arthropod hemocyanins [48] "
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    • "Similar to the structures of FUs in native HdH1 (PDB ID: 3J32) [23], all FUs of isomeric HdH1 contain two structural domains, the N-terminal core domain, which predominantly consists of α-helices, and the C-terminalβsheet domain, which contains theβsheets region (dashed lines in Fig. S3). FU_H, which locates in the end and forms the slab of cylindrical decamers (Fig. 1B and 1D, magenta domains), is structurally unique among all of the FUs of HdH1 as it has an additional cupredoxin-like fold (Fig S2, sequence underlined and Fig. S3, red densities) [28], [29]. All of the built pseudoatomic models of isomeric FUs fit well with the corresponding density maps of isomeric HdH1, while the α helices,βsheets and the loops of each FU can be accommodated precisely in the density maps (Fig. S3). "
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    • "FUs are typically 50 kDa in size, however, FU-h contains an additional stretch of $100 amino acids (cupredoxin-like domain) located at the C-terminal end of the polypeptide, bringing the total molecular weight of FU-h to $60 kDa (Lieb et al., 2000; Jaenicke et al., 2010). Each FU is ordinarily composed of two domains, the a-domain consisting of a four a-helix bundle that houses the di-copper centre and the b-domain incorporating a seven stranded anti-parallel b-barrel (Fig. 2). "
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