Assembly of alpha- and beta-subunits in the endoplasmic reticulum is a prerequisite for the structural and functional maturation of oligomeric P-type ATPases. In Xenopus oocytes, overexpressed, unassembled alpha- and beta-subunits of Xenopus Na,K-ATPase are retained in the endoplasmic reticulum (ER) and are degraded with different kinetics, while unassembled beta-subunits of gastric H, K-ATPase leave the ER. In this study, we have investigated the role of the immunoglobulin-binding protein, BiP, in the folding, assembly, and ER retention of ATPase subunits. We determined the primary sequence of Xenopus BiP and used polyclonal antibodies to examine the interaction with BiP of various wild type and mutant alpha- and beta-subunits overexpressed in Xenopus oocytes. Our results show that ER-retained, unassembled Na,K-ATPase beta-subunits, but not transport-competent H,K-ATPase beta-subunits, efficiently associate with BiP until assembly with alpha-subunits occurs. Furthermore, the kinetics of BiP interaction with unassembled wild type and with mutant Na,K-ATPase beta-subunits parallels their respective stability against cellular degradation. Finally, alpha-subunits that are overexpressed in oocytes and are rapidly degraded and endogenous oocyte alpha-subunits that are stably expressed as individual assembly-competent proteins also interact with oocyte or exogenous BiP, and the interaction time correlates with the protein's stability. These data demonstrate for the first time that BiP might be involved in a long term maturation arrest and/or in the ER quality control of a multimembrane-spanning protein and lend support for a universal chaperone function of BiP.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.271.34.20895 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ADP-inhibited structure of non-catalytic site-depleted FF-ATPase from thermophilic Bacillus sp. PS-3.
Biochim Biophys Acta Bioenerg
January 2025
Department of Molecular Biosciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan. Electronic address:
The F domain of FF-ATP synthases/ATPases (FF) possesses three catalytic sites on the three αβ interfaces, termed αβ, αβ, and αβ, located mainly on the β subunits. The enzyme also has three non-catalytic ATP-binding sites on the three αβ interfaces, located mainly on the α subunits. When ATP does not bind to the non-catalytic site, FF becomes significantly prone to ADP inhibition, ultimately resulting in the loss of ATPase activity.
View Article and Find Full Text PDFMechanism of female CHH caused by compound heterozygous mutations in the LHB gene.
J Assist Reprod Genet
January 2025
Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, School of Basic Medicine, Center of Excellence in Tissue Engineering of Chinese Academy of Medical Sciences, Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory, PekingBeijing, 100730, China.
Background: Luteinizing hormone (LH) plays a crucial role in the postnatal development and maturation of gonads. Inactivating mutations of the luteinizing hormone beta subunit (LHB)gene are extremely rare and can result in congenital hypogonadotropic hypogonadism (CHH).
Methods: We conducted DNA sequencing on an 18-year-old female patient with undetectable LH and clinical symptoms of CHH.
Genetic variants of accessory proteins and G proteins in human genetic disease.
Crit Rev Clin Lab Sci
January 2025
Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, West Midlands, UK.
We present a series of three articles on the genetics and pharmacogenetics of G protein- coupled receptors (GPCR). In the first article, we discuss genetic variants of the G protein subunits and accessory proteins that are associated with human phenotypes; in the second article, we build upon this to discuss "G protein-coupled receptor (GPCR) gene variants and human genetic disease" and in the third article, we survey "G protein-coupled receptor pharmacogenomics". In the present article, we review the processes of ligand binding, GPCR activation, inactivation, and receptor trafficking to the membrane in the context of human genetic disease resulting from pathogenic variants of accessory proteins and G proteins.
View Article and Find Full Text PDFObesity-induced activation of NADPH oxidase 2 prolongs cardiac repolarization via inhibiting K+ currents.
PLoS One
December 2024
Chinese PLA Medical School, Chinese PLA General Hospital, Beijing, China.
Obesity is associated with abnormal repolarization manifested by QT interval prolongation, and oxidative stress is an important link between obesity and arrhythmias. However, the underlying electrophysiological and molecular mechanisms remain unclear. The aim of this study is to evaluate the role of obesity in potassium current in ventricular myocytes and the potential mechanism of NADPH oxidase 2 (Nox2).
View Article and Find Full Text PDFMolecular basis of hemoglobin binding and heme removal in .
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.
To successfully mount infections, nearly all bacterial pathogens must acquire iron, a key metal cofactor that primarily resides within human hemoglobin. causes the life-threatening respiratory disease diphtheria and captures hemoglobin for iron scavenging using the surface-displayed receptor HbpA. Here, we show using X-ray crystallography, NMR, and in situ binding measurements that selectively captures iron-loaded hemoglobin by partially ensconcing the heme molecules of its α subunits.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!