SEARCH:   Advanced

Blood, 15 February 2006, Vol. 107, No. 4, pp. 1284-1291. Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-08-3112. This Article Full Text (PDF) All Versions of this Article: 2005-08-3112v1 107/4/1284    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ottersbach, K. Articles by Graham, G. J Search for Related Content PubMed PubMed Citation Articles by Ottersbach, K. Articles by Graham, G. J Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 3, 2005 Accepted October 3, 2005 A 310 helical turn is essential for the proliferative-inhibitory properties of macrophage inflammatory protein-1 alpha (CCL3) Katrin Ottersbach, John Mclean, Neil W Isaacs, and Gerard J Graham* Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, Scotland, United Kingdom Department of Chemistry, University of Glasgow, Glasgow, Scotland, United Kingdom * Corresponding author; email: g.graham{at}clinmed.gla.ac.uk. Despite possessing marked structural similarities, the chemokines MIP-1 and RANTES display differential activity in haemopoietic progenitor cell inhibitory assays, with MIP-1 being active and RANTES inactive in this context. We have sought to identify the key structural determinants of this property of MIP-1. This has involved constructing MIP-1/RANTES chimaeras by swapping structural domains between the two proteins. Results indicate that, in contrast to other chemokine functions, neither the N nor the C termini are key determinants of inhibitory activity. The motif that appears to be most important for this activity lies between the 2nd and 4th cysteines of MIP-1 and further domain swap analysis has narrowed this down to the 310 helical turn preceding the first -strand in MIP-1. More detailed analysis has highlighted the role played by a specific dipeptide motif in the proliferation-inhibitory activity of chemokines. The involvement of the 310 helical turn motif in chemokine function is unprecedented and this study therefore identifies a novel functionally essential motif within chemokines. In addition, this study further attests to the alternative mechanisms of action used by MIP-1 in inhibition of haemopoietic progenitor cell proliferation and regulation of leukocyte migration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A helical turn makes an attractive inhibitor Charlie Mantel Blood 2006 107: 1245-1246. [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020