Biochemistry, Department of


Date of this Version



The Journal of Biological Chemistry, VOL. 283, NO. 22, pp. 15015–15022, May 30, 2008


© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.


Sco1 is implicated in the copper metallation of the CuA site in

Cox2 of cytochrome oxidase. The structure of Sco1 in the metallated

and apo-conformers revealed structural dynamics primarily

in an exposed region designated loop 8. The structural

dynamics of loop 8 in Sco1 suggests it may be an interface for

interactions with Cox17, the Cu(I) donor and/or Cox2. A series

of conserved residues in the sequence motif 217KKYRVYF223 on

the leading edge of this loop are shown presently to be important

for yeast Sco1 function. Cells harboring Y219D, R220D, V221D,

and Y222D mutant Sco1 proteins failed to restore respiratory

growth or cytochrome oxidase activity in sco1∆ cells. The

mutant proteins are stably expressed and are competent to bind

Cu(I) and Cu(II) normally. Specific Cu(I) transfer from Cox17 to

the mutant apo-Sco1 proteins proceeds normally. In contrast,

using two in vivo assays that permit monitoring of the transient

Sco1-Cox2 interaction, the mutant Sco1 molecules appear compromised

in a function with Cox2. The mutants failed to suppress

the respiratory defect of cox17-1 cells unlike wild-type

SCO1. In addition, the mutants failed to suppress the hydrogen

peroxide sensitivity of sco1∆ cells. These studies implicate different

surfaces on Sco1 for interaction or function with Cox17

and Cox2.