TY  - GEN
AB  - Copper‑transporting ATPases ATP7A and ATP7B use six N‑terminal metal‑binding domains (MBDs) to sense cytosolic copper, but how these domains coordinate regulation is unclear. Using biochemical and computational methods, we show that ATP7B’s MBDs form a compact structure that undergoes major reorganization with copper binding or CxxC mutation. MBD2 appears to be the primary copper‑accepting site from ATOX1, with MBD4 and MBD6 acting downstream. ATP7B shows cooperative structural changes not observed in ATP7A, and disease‑associated mutations alter copper‑transfer behavior. These findings support a model in which inter‑MBD loops mediate copper‑dependent conformational signaling.
AD  - Oregon Health and Science University
AU  - LeShane, Erik
DA  - 2010
DO  - 10.6083/M4J67DXK
DO  - DOI
ED  - Lutsenko, Svetlana
ED  - Mentor
ID  - 552
KW  - Adenosine Triphosphatases
KW  - Molecular Chaperones
KW  - Proteins
KW  - Copper
KW  - Oxidation-Reduction
KW  - Mutation
KW  - Menkes Kinky Hair Syndrome
KW  - Copper-Transporting ATPases
KW  - Humans
KW  - Protein Structure, Quaternary
KW  - menkes disease protein
KW  - protein structure
KW  - wilson disease protein
KW  - atox1 protein
KW  - oxidation-reduction reaction
L1  - https://digitalcollections.ohsu.edu/record/552/files/553_etd.pdf
L2  - https://digitalcollections.ohsu.edu/record/552/files/553_etd.pdf
L4  - https://digitalcollections.ohsu.edu/record/552/files/553_etd.pdf
LK  - https://digitalcollections.ohsu.edu/record/552/files/553_etd.pdf
N2  - Copper‑transporting ATPases ATP7A and ATP7B use six N‑terminal metal‑binding domains (MBDs) to sense cytosolic copper, but how these domains coordinate regulation is unclear. Using biochemical and computational methods, we show that ATP7B’s MBDs form a compact structure that undergoes major reorganization with copper binding or CxxC mutation. MBD2 appears to be the primary copper‑accepting site from ATOX1, with MBD4 and MBD6 acting downstream. ATP7B shows cooperative structural changes not observed in ATP7A, and disease‑associated mutations alter copper‑transfer behavior. These findings support a model in which inter‑MBD loops mediate copper‑dependent conformational signaling.
PB  - Oregon Health and Science University
PY  - 2010
T1  - Structural organization and mechanisms of cooperativity in the N-Terminal domains of human CU-ATpases
TI  - Structural organization and mechanisms of cooperativity in the N-Terminal domains of human CU-ATpases
UR  - https://digitalcollections.ohsu.edu/record/552/files/553_etd.pdf
Y1  - 2010
ER  -