The Affinity of a Major Ca2+ Binding Site on GRP78 Is Differentially Enhanced by ADP and ATP

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dc.contributor.author Lamb, HK
dc.contributor.author Mee, C
dc.contributor.author Xu, W
dc.contributor.author Liu, L
dc.contributor.author Blond, S
dc.contributor.author Cooper, A
dc.contributor.author Charles, IG
dc.contributor.author Hawkins, AR
dc.date.accessioned 2011-02-07T06:20:10Z
dc.date.issued 2006-01
dc.identifier.citation Journal of Biological Chemistry, 2006, 281 (13), pp. 8796 - 8805
dc.identifier.issn 0021-9258
dc.identifier.other C1UNSUBMIT en_US
dc.identifier.uri http://hdl.handle.net/10453/13250
dc.description.abstract GRP78 is a major protein regulated by the mammalian endoplasmic reticulum stress response, and up-regulation has been shown to be important in protecting cells from challenge with cytotoxic agents. GRP78 has ATPase activity, acts as a chaperone, and interacts specifically with other proteins, such as caspases, as part of a mechanism regulating apoptosis. GRP78 is also reported to have a possible role as a Ca2+ storage protein. In order to understand the potential biological effects of Ca2+ and ATP/ADP binding on the biology of GRP78, we have determined its ligand binding properties. We show here for the first time that GRP78 can bind Ca2+, ATP, and ADP, each with a 1:1 stoichiometry, and that the binding of cation and nucleotide is cooperative. These observations do not support the hypothesis that GRP78 is a dynamic Ca2+ storage protein. Furthermore, we demonstrate that whereas Mg2+ enhances GRP78 binding to ADP and ATP to the same extent, Ca2+ shows a differential enhancement. In the presence of Ca2+, the KD for ATP is lowered ?11-fold, and the KD for ADP is lowered around 930-fold. The KD for Ca2+ is lowered ?40-fold in the presence of ATP and around 880-fold with ADP. These findings may explain the biological requirement for a nucleotide exchange factor to remove ADP from GRP78. Taken together, our data suggest that the Ca2+-binding property of GRP78 may be part of a signal transduction pathway that modulates complex interactions between GRP78, ATP/ADP, secretory proteins, and caspases, and this ultimately has important consequences for cell viability.
dc.format Scott McWhirter
dc.publisher ASBMB
dc.relation.isbasedon 10.1074/jbc.M503964200
dc.title The Affinity of a Major Ca2+ Binding Site on GRP78 Is Differentially Enhanced by ADP and ATP
dc.type Journal Article
dc.parent Journal of Biological Chemistry
dc.journal.volume 13
dc.journal.volume 281
dc.journal.number 13 en_US
dc.publocation USA en_US
dc.identifier.startpage 8796 en_US
dc.identifier.endpage 8805 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 0605 Microbiology
dc.personcode 109028
dc.percentage 100 en_US
dc.classification.name Microbiology en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords NA en_US
dc.description.keywords NA
dc.description.keywords NA
dc.description.keywords NA
dc.description.keywords NA
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Strength - i3
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10


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