Yeast Cox17 Solution Structure and Copper(I) Binding

Abajian, C.; Yatsunyk, Liliya A.; Ramirez, Benjamin E.; Rosenzweig, Amy C.

doi:10.1074/jbc.m408099200

Cited by 101 publications

(78 citation statements)

References 58 publications

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“…Extracellular Cu(II) is largely bound to ceruloplasmin and serum albumin in addition to lower molecular weight chelators such as amino acids. The high affinity Cu(II) site of serum albumin has been measured in the range 10 11.1 -10 , respectively (28,26). In contrast, the Cu(II) binding affinity of PrP is higher than these copper chaperones, which probably achieve specific delivery of the metal by kinetic control through a slow k off rather than a high affinity constant.…”

Section: Discussionmentioning

confidence: 99%

High Affinity Binding between Copper and Full-length Prion Protein Identified by Two Different Techniques

Thompsett

Abdelraheim

Daniels

et al. 2005

Journal of Biological Chemistry

113

134

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The cellular prion protein is known to be a copper-binding protein. Despite the wide range of studies on the copper binding of PrP, there have been no studies to determine the affinity of the protein on both full-length prion protein and under physiological conditions. We have used two techniques, isothermal titration calorimetry and competitive metal capture analysis, to determine the affinity of copper for wild type mouse PrP and a series of mutants. The cellular prion protein PrP c is a cell surface glycoprotein with large ␣-helical content that is attached to the plasma membrane by a glycosylphosphatidylinositol anchor. This cellular form of the protein binds copper, and it is argued that this copper binding to PrP c is intimately linked to the normal cellular function of the protein either in copper transport, sequestration, or antioxidant activity (1-3). The native cellular protein may undergo a conformational transformation to a proteaseresistant species known as a prion (PrP Sc ) with high ␤-sheet content and a tendency to aggregate. This transformed species is the putative proteinaceous infectious agent of transmissible spongiform encephalopathies or prion diseases (4). Prion diseases are characterized by a metal imbalance in the brain that occurs simultaneously to conversion of PrP c to PrPSc . The metal imbalance is associated with the loss of copper binding from PrP c on conversion to PrP Sc (5, 6). This raises important questions concerning the role of copper and other metals in prion diseases. Loss of protein function as a result of impaired copper binding in diseased PrPSc could have serious implications for disease progression.As a result, knowledge of copper binding to PrP is important in considering both the normal function of PrP c and its influence in prion diseases.Although it is accepted that PrP c is a Cu(II) binding protein, there are many facets of the interaction of Cu(II) and PrP c that are disputed. These include the exact number of binding sites and their relative affinity for Cu(II). Initial studies focused on a fragment of the protein termed the octameric repeat region because it contains four repeats of an octamer. This region contains histidine and so was a likely candidate for the binding site. These early studies (7, 8) suggested Cu(II) binds to this region with a micromolar affinity that was little more specific than histidine on its own. Further studies with larger fragments also suggested that Cu(II) binds PrP c , but again the affinity seen was similarly a low micromolar association (9). A study of the effect of PrP c expression on Cu(II) uptake into cells suggested that the affinity must at least be in the nanomolar range (1). Nanomolar affinities for the octameric repeat region have rarely been suggested (10). Only one publication has suggested that the affinity of Cu(II) for PrP is in the femtomolar range (11). Although such a high affinity implies that PrP is a very specific Cu(II)-binding protein, this finding has never been reproduced. Therefore, there is currently no...

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Section: Discussionmentioning

confidence: 99%

High Affinity Binding between Copper and Full-length Prion Protein Identified by Two Different Techniques

Thompsett

Abdelraheim

Daniels

et al. 2005

Journal of Biological Chemistry

113

134

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“…Cox17 can exist in two distinct Cu(I) conformers. One conformer consists of a single Cu(I) coordinated to a monomeric protein stabilized by two disulfide bonds (10). Coordination of a single Cu(I) ion in Cox17 requires isomerization of the disulfides such that one disulfide consisting of Cys 26 /Cys 57 is converted to a Cys 24 / Cys 57 disulfide prior to Cu(I) binding (8).…”

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confidence: 99%

Characterization of the Cytochrome c Oxidase Assembly Factor Cox19 of Saccharomyces cerevisiae

Rigby

Zhang

Cobine

et al. 2007

Journal of Biological Chemistry

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“…NMR also provided the first structures of human and yeast Cox17 (Abajian et al, 2004;Arnesano et al, 2005;Banci et al, 2008c) (Fig. 6) as well as direct evidence how metal transfer processes from Cu(I)Cox17 toward both human Sco1 and Sco2 work at the molecular level (Banci et al, 2007e;Banci et al, 2008b), suggesting that the partially oxidized Cu(I)Cox17 is the functional metallochaperone species in the IMS.…”

Section: Copper"i… In the Mitochondria: Cco Assemblymentioning

confidence: 89%

Copper trafficking in biology: An NMR approach

2009

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Copper ions are essential for living organisms because they are involved in several fundamental biological processes. Biomolecules interacting with copper ions have to be characterized as such, when bound to the metal ion, and when they interact with other biomolecules or substrates. The characterization is both structural and dynamic. In this context, NMR is a preferred tool of investigation because it allows shedding light on what happens in solution. Here, the NMR contribution to the copper trafficking is described, providing precious information on biochemical pathways, which are essential to understand the mechanisms of life at the molecular level.

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Yeast Cox17 Solution Structure and Copper(I) Binding

Cited by 101 publications

References 58 publications

High Affinity Binding between Copper and Full-length Prion Protein Identified by Two Different Techniques

High Affinity Binding between Copper and Full-length Prion Protein Identified by Two Different Techniques

Characterization of the Cytochrome c Oxidase Assembly Factor Cox19 of Saccharomyces cerevisiae

Copper trafficking in biology: An NMR approach

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