8ZYJ

Cryo-EM structure of human testis-specific Na+,K+-ATPase alpha4 in ouabain-bound form

Summary for 8ZYJ

• Entry DOI: 10.2210/pdb8zyj/pdb
• EMDB information: 60570
• Descriptor: Sodium/potassium-transporting ATPase subunit alpha-4, Sodium/potassium-transporting ATPase subunit beta-1, MAGNESIUM ION, ... (10 entities in total)
• Functional Keywords: p-type atpase, sodium pump, na+, k+-atpase, testis, human, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 149851.07

Authors

Abe, K.,Blanco, G. (deposition date: 2024-06-18, release date: 2024-12-04, Last modification date: 2024-12-11)

Primary citation

Abe, K.,McDermott, J.,Valia Madapally, H.,Marimuthu, P.,Gopalasingam, C.C.,Gerle, C.,Shigematsu, H.,Khandelia, H.,Blanco, G.
Molecular Structure of the Na + ,K + -ATPase alpha 4 beta 1 Isoform in Its Ouabain-Bound Conformation.
Int J Mol Sci, 25:-, 2024

PubMed Abstract: Na,K-ATPase is the active ion transport system that maintains the electrochemical gradients for Na and K across the plasma membrane of most animal cells. Na,K-ATPase is constituted by the association of two major subunits, a catalytic α and a glycosylated β subunit, both of which exist as different isoforms (in mammals known as α1, α2, α3, α4, β1, β2 and β3). Na,K-ATPase α and β isoforms assemble in different combinations to produce various isozymes with tissue specific expression and distinct biochemical properties. Na,K-ATPase α4β1 is only found in male germ cells of the testis and is mainly expressed in the sperm flagellum, where it plays a critical role in sperm motility and male fertility. Here, we report the molecular structure of Na,K-ATPase α4β1 at 2.37 Å resolution in the ouabain-bound state and in the presence of beryllium fluoride. Overall, Na,K-ATPase α4 structure exhibits the basic major domains of a P-Type ATPase, resembling Na,K-ATPase α1, but has differences specific to its distinct sequence. Dissimilarities include the site where the inhibitor ouabain binds. Molecular simulations indicate that glycosphingolipids can bind to a putative glycosphingolipid binding site, which could potentially modulate Na,K-ATPase α4 activity. This is the first experimental evidence for the structure of Na,K-ATPase α4β1. These data provide a template that will aid in better understanding the function Na,K-ATPase α4β1 and will be important for the design and development of compounds that can modulate Na,K-ATPase α4 activity for the purpose of improving male fertility or to achieve male contraception.

PubMed: 39596464
DOI: 10.3390/ijms252212397

Experimental method

ELECTRON MICROSCOPY (2.37 Å)