Neurological disease mutations of α3 Na+,K+-ATPase: Structural and functional perspectives and rescue of compromised function

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisReviewForskningpeer review

Abstract

Na +,K +-ATPase creates transmembrane ion gradients crucial to the function of the central nervous system. The α-subunit of Na +,K +-ATPase exists as four isoforms (α1–α4). Several neurological phenotypes derive from α3 mutations. The effects of some of these mutations on Na +,K +-ATPase function have been studied in vitro. Here we discuss the α3 disease mutations as well as information derived from studies of corresponding mutations of α1 in the light of the high-resolution crystal structures of the Na +,K +-ATPase. A high proportion of the α3 disease mutations occur in the transmembrane sector and nearby regions essential to Na + and K + binding. In several cases the compromised function can be traced to disturbance of the Na + specific binding site III. Recently, a secondary mutation was found to rescue the defective Na + binding caused by a disease mutation. A perspective is that it may be possible to develop an efficient pharmaceutical mimicking the rescuing effect.

OriginalsprogEngelsk
TidsskriftB B A - Bioenergetics
Vol/bind1857
Nummer11
Sider (fra-til)1807–1828
Antal sider22
ISSN0005-2728
DOI
StatusUdgivet - nov. 2016

Fingeraftryk

Dyk ned i forskningsemnerne om 'Neurological disease mutations of α3 Na+,K+-ATPase: Structural and functional perspectives and rescue of compromised function'. Sammen danner de et unikt fingeraftryk.

Citationsformater