16774914

Source:http://linkedlifedata.com/resource/pubmed/id/16774914

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0007577, umls-concept:C0042971, umls-concept:C0086816, umls-concept:C0851285, umls-concept:C1517773
pubmed:issue	36
pubmed:dateCreated	2006-9-4
pubmed:abstractText	Glycoprotein (GP) Ib-IX-V binds von Willebrand factor (VWF), initiating thrombosis at high shear stress. The VWF-A1 domain binds the N-terminal domain of GPIbalpha (His1-Glu282); this region contains seven leucine-rich repeats (LRR) plus N- and C-terminal flanking sequences and an anionic sequence containing three sulfated tyrosines. Our previous analysis of canine/human and human/canine chimeras of GPIbalpha expressed on Chinese hamster ovary (CHO) cells demonstrated that LRR2-4 (Leu60-Glu128) were crucial for GPIbalpha-dependent adhesion to VWF. Paradoxically, co-crystal structures of the GPIbalpha N-terminal domain and GPIbalpha-binding VWF-A1 under static conditions revealed that the LRR2-4 sequence made minimal contact with VWF-A1. To resolve the specific functional role of LRR2-4, we compared wild-type human GPIbalpha with human GPIbalpha containing a homology domain swap of canine for human sequence within Leu60-Glu128 and a reverse swap (canine GPIbalpha with human Leu60-Glu128) for the ability to support adhesion to VWF under flow. Binding of conformation-specific anti-GPIbalpha antibodies and VWF binding in the presence of botrocetin (which does not discriminate between species) confirmed equivalent expression of wild-type and mutant receptors in a functional form competent to bind ligand. Compared with CHO cells expressing wild-type GPIbalpha, cells expressing GPIbalpha, where human Leu60-Glu128 sequence was replaced by canine sequence, supported adhesion to VWF at low shear rates but became increasingly ineffective as shear increased from 50 to 2000 s(-1). Together, these data demonstrate that LRR2-4, encompassing a pronounced negative charge patch on human GPIbalpha, is essential for GPIbalpha.VWF-dependent adhesion as hydrodynamic shear increases.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/2985121R
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Crotalid Venoms, http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Hemagglutinins, http://linkedlifedata.com/resource/pubmed/chemical/Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/adhesion receptor, http://linkedlifedata.com/resource/pubmed/chemical/botrocetin, http://linkedlifedata.com/resource/pubmed/chemical/leucine-rich repeat proteins, http://linkedlifedata.com/resource/pubmed/chemical/von Willebrand Factor
pubmed:status	MEDLINE
pubmed:month	Sep
pubmed:issn	0021-9258
pubmed:author	pubmed-author:AndrewsRobert KRK, pubmed-author:ApricoAndreaA, pubmed-author:BerndtMichael CMC, pubmed-author:CranmerSusan LSL, pubmed-author:JacksonShaun PSP, pubmed-author:ShenYangY, pubmed-author:WhisstockJames CJC
pubmed:issnType	Print
pubmed:day	8
pubmed:volume	281
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	26419-23
pubmed:dateRevised	2009-11-19
pubmed:meshHeading	pubmed-meshheading:16774914-Animals, pubmed-meshheading:16774914-CHO Cells, pubmed-meshheading:16774914-Cell Adhesion, pubmed-meshheading:16774914-Cricetinae, pubmed-meshheading:16774914-Crotalid Venoms, pubmed-meshheading:16774914-Dogs, pubmed-meshheading:16774914-Glutamic Acid, pubmed-meshheading:16774914-Hemagglutinins, pubmed-meshheading:16774914-Humans, pubmed-meshheading:16774914-Leucine, pubmed-meshheading:16774914-Membrane Glycoproteins, pubmed-meshheading:16774914-Membrane Proteins, pubmed-meshheading:16774914-Models, Molecular, pubmed-meshheading:16774914-Protein Conformation, pubmed-meshheading:16774914-Proteins, pubmed-meshheading:16774914-Recombinant Fusion Proteins, pubmed-meshheading:16774914-Repetitive Sequences, Amino Acid, pubmed-meshheading:16774914-Shear Strength, pubmed-meshheading:16774914-von Willebrand Factor
pubmed:year	2006
pubmed:articleTitle	Leucine-rich repeats 2-4 (Leu60-Glu128) of platelet glycoprotein Ibalpha regulate shear-dependent cell adhesion to von Willebrand factor.
pubmed:affiliation	Department of Immunology and the Department of Biochemistry and Molecular Biology, Monash University, Victoria, 3800, Australia.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't