Linked Life Data

16533065

Source:http://linkedlifedata.com/resource/pubmed/id/16533065

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-3-14
pubmed:abstractText
We report here a novel regulation of the ATPase activity of the human retina specific ATP binding cassette transporter (ABC), ABCR, by nucleotide binding domain interactions. We also present evidence that recombinant nucleotide binding domains of ABCR interact in vitro in the complete absence of transmembrane domains (TMDs). Although similar domain-domain interactions have been described in other ABC transporters, the roles of such interactions on the enzymatic mechanisms of these transporters have not been demonstrated experimentally. A quantitative analysis of the in vitro interactions as a function of the nucleotide-bound state demonstrated that the interaction takes place in the absence of nucleotide as well as in the presence of ATP and that it only attenuates in the ADP-bound state. Analysis of the ATPase activities of these proteins in free and complex states indicated that the NBD1-NBD2 interaction significantly influences the ATPase activity. Further investigation, using site-specific mutants, showed that mutations in NBD2 but not NBD1 led to the alteration of the ATPase activity of the NBD1.NBD2 complex and residue Arg 2038 is critical to this regulation. These data indicate that changes in the oligomeric state of the nucleotide binding domains of ABCR are coupled to ATP hydrolysis and might represent a possible signal for the TMDs of ABCR to export the bound substrate. Furthermore, the data support a mechanistic model in which, upon binding of NBD2, NBD1 binds ATP but does not hydrolyze it or does so with a significantly reduced rate.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3813-23
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16533065-ATP-Binding Cassette Transporters, pubmed-meshheading:16533065-Adenosine Diphosphate, pubmed-meshheading:16533065-Adenosine Triphosphatases, pubmed-meshheading:16533065-Binding Sites, pubmed-meshheading:16533065-Carrier Proteins, pubmed-meshheading:16533065-Fluorescence Polarization, pubmed-meshheading:16533065-Gene Expression Regulation, Enzymologic, pubmed-meshheading:16533065-Humans, pubmed-meshheading:16533065-Hydrolysis, pubmed-meshheading:16533065-Kinetics, pubmed-meshheading:16533065-Models, Biological, pubmed-meshheading:16533065-Mutation, pubmed-meshheading:16533065-Peptides, pubmed-meshheading:16533065-Protein Binding, pubmed-meshheading:16533065-Protein Structure, Tertiary, pubmed-meshheading:16533065-Recombinant Proteins, pubmed-meshheading:16533065-Retina
pubmed:year
2006
pubmed:articleTitle
Interaction of the nucleotide binding domains and regulation of the ATPase activity of the human retina specific ABC transporter, ABCR.
pubmed:affiliation
Department of Bioscience Technologies, Program in Biotechnology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Esther.Biswas@jefferson.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural