Linked Life Data

15134651

Source:http://linkedlifedata.com/resource/pubmed/id/15134651

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-5-11
pubmed:abstractText
The specific localization of the asymmetric form of acetylcholinesterase (AChE) in neuromuscular junctions results from the interaction of its collagen-like tail with heparan sulfate proteoglycans in the synaptic basal lamina. This interaction involves two heparin binding consensus sequences of the form XBBXB, where B is a basic residue, located in the triple-helical collagen tail: GRKGR for the N-terminal site and GKRGK for the C-terminal site. To explore the basis of the higher heparin affinity seen for the C-terminal site vs. the N-terminal site, two homologous series of (Gly-Xaa-Yaa)(8) peptides were constructed to model these triple-helical binding sites. Individual tripeptide units from each heparin binding site were introduced in a stepwise fashion into a Gly-Pro-Hyp framework, until the consensus sequence and its surrounding triplets were recreated. As each additional triplet from the binding site is inserted to replace a host Gly-Pro-Hyp triplet, the triple-helix stability decreases, and the drop in thermal stability is close to that expected if each Gly-X-Y triplet contributed independently to global stability. CD spectroscopy and calorimetry show the stability of these AChE model peptides is increased by addition of heparin, confirming binding to heparin, and the lack of significant enthalpy change indicates the binding is largely electrostatic in nature. Displacement assays measure the strength of the peptide-heparin interaction, and indicate an inverse correlation between the peptide ability to bind heparin and its thermal stability. The model peptides for the C-terminal binding site show a greater heparin affinity than the peptide models for the N-terminal binding site only when residues surrounding the consensus sequence are included.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
1698
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
187-95
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Stepwise construction of triple-helical heparin binding sites using peptide models.
pubmed:affiliation
Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't