Linked Life Data

11570883

Source:http://linkedlifedata.com/resource/pubmed/id/11570883

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2001-9-25
pubmed:abstractText
Clusterin is a heterodimeric glycoprotein found in many tissues of the body and is the most abundant protein secreted by cultured rat Sertoli cells. The function of clusterin is unknown, but it has been associated with cellular injury, lipid transport, apoptosis, and it may be involved in the clearance of cellular debris caused by cell injury or death. Consistent with this last idea, clusterin has been shown to bind to a variety of molecules with high affinity including lipids, peptides, and proteins and the hydrophobic probe 1-anilino-8-naphthalenesulfonate (ANS). Given this variety of ligands, clusterin must have specific structural features that provide the protein with its promiscuous binding activity. Using sequence analyses, we show that clusterin likely contains three long regions of natively disordered or molten globule-like structures containing putative amphipathic alpha-helices. These disordered regions were highly sensitive to trypsin digestion, indicating a flexible nature. The effects of denaturation on the fluorescence of the clusterin-ANS complex were compared between proteins with structured binding pockets and molten globular forms of proteins. Clusterin bound ANS in a manner that was very similar to that of molten globular proteins. Furthermore, we found that, when bound to ANS, at least one cleavage site within the protease-sensitive disordered regions of clusterin was protected from trypsin digestion. In addition, we show that clusterin can function as a biological detergent that can solubilize bacteriorhodopsin. We propose that natively disordered regions with amphipathic helices form a dynamic, molten globule-like binding site and provide clusterin the ability to bind to a variety of molecules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11828-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Clusterin, a binding protein with a molten globule-like region.
pubmed:affiliation
School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4660,USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.