Linked Life Data

12188899

Source:http://linkedlifedata.com/resource/pubmed/id/12188899

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-8-21
pubmed:abstractText
The large, multifunctional proteins Factors V and VIII are cofactors in the coagulation cascade and possess a similar domain structure, A1-A2-B-A3-C1-C2. The C domains are related to the discoidin protein family, while the A domains are homologous to the copper-binding protein ceruloplasmin. After proteolytic activation, Factors V and VIII behave as peripheral membrane proteins, binding to negatively charged membranes containing phosphatidylserine, primarily via specific sites on their C2 domains. This type of membrane surface is exposed at sites of tissue damage, where platelets have become activated. The cofactors then accelerate sequential proteolytic activations that occur at critical control points in the blood coagulation cascade via complex formation with specific serine proteinases. Here we compare recent structural and functional studies of the C2 domains of Factors V and VIII, and discuss their respective roles. The membrane-binding motifs consist of several exposed hydrophobic side chains surrounded by a ring of basic residues, and the C2 domains appear poised to insert their hydrophobic "feet" into the membrane interior as basic residues interact favorably with phosphatidylserine head groups. In line with their physiological roles, the membrane-binding surfaces of the C2 domains display a good deal of mobility. We then extend our analysis to other members of the discoidin protein family, which perform diverse physiological functions involving signaling pathways at cell surfaces. Finally, structural similarities between discoidin proteins and the topologically distinct but functionally related membrane-binding "classic C2 domains", including signal-transduction proteins such as Protein Kinase C and phospholipases, are noted.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1389-2037
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
313-39
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
New insights into binding interfaces of coagulation factors V and VIII and their homologues lessons from high resolution crystal structures.
pubmed:affiliation
Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18, Martinsried, D-82152, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't