000000552 001__ 552 000000552 005__ 20260410124448.0 000000552 0247_ $$2DOI$$a10.6083/M4J67DXK 000000552 037__ $$aETD 000000552 245__ $$aStructural organization and mechanisms of cooperativity in the N-Terminal domains of human CU-ATpases 000000552 260__ $$bOregon Health and Science University 000000552 269__ $$a2010 000000552 336__ $$aDissertation 000000552 502__ $$bPh.D. 000000552 520__ $$aCopper‑transporting ATPases ATP7A and ATP7B use six N‑terminal metal‑binding domains (MBDs) to sense cytosolic copper, but how these domains coordinate regulation is unclear. Using biochemical and computational methods, we show that ATP7B’s MBDs form a compact structure that undergoes major reorganization with copper binding or CxxC mutation. MBD2 appears to be the primary copper‑accepting site from ATOX1, with MBD4 and MBD6 acting downstream. ATP7B shows cooperative structural changes not observed in ATP7A, and disease‑associated mutations alter copper‑transfer behavior. These findings support a model in which inter‑MBD loops mediate copper‑dependent conformational signaling. 000000552 540__ $$fCC BY 000000552 542__ $$fIn copyright - single owner 000000552 650__ $$aAdenosine Triphosphatases$$014245 000000552 650__ $$aMolecular Chaperones$$031132 000000552 650__ $$aProteins$$024763 000000552 650__ $$aCopper$$017086 000000552 650__ $$aOxidation-Reduction$$023418 000000552 650__ $$aMutation$$022555 000000552 650__ $$aMenkes Kinky Hair Syndrome$$021220 000000552 650__ $$aCopper-Transporting ATPases$$012204 000000552 650__ $$aHumans 000000552 650__ $$aProtein Structure, Quaternary$$032743 000000552 6531_ $$amenkes disease protein 000000552 6531_ $$aprotein structure 000000552 6531_ $$awilson disease protein 000000552 6531_ $$aatox1 protein 000000552 6531_ $$aoxidation-reduction reaction 000000552 691__ $$aSchool of Medicine$$041369 000000552 692__ $$aDepartment of Molecular and Medical Genetics$$041428 000000552 7001_ $$aLeShane, Erik$$uOregon Health and Science University$$041354 000000552 7201_ $$aLutsenko, Svetlana$$uJohns Hopkins School of Medicine$$7Personal$$eMentor 000000552 8564_ $$92920996d-5c0b-4620-86c1-42822ba7d7a0$$s4679160$$uhttps://digitalcollections.ohsu.edu/record/552/files/553_etd.pdf$$ePublic$$2de43cfa35834b55139943ad533a0c11a$$31 000000552 901__ $$a<p>These documents are archival records. They are retained for historical reference only. </p><p><b>Need an accessible version? Use the ‘Get Accessible Copy’ link above.</b></p> 000000552 905__ $$a/rest/prod/m3/26/m1/73/m326m173p 000000552 909CO $$ooai:digitalcollections.ohsu.edu:552$$pstudent-work 000000552 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000000552 980__ $$aTheses and Dissertations