HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 51, 42207-42218, December 23, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/51/42207    most recent M510407200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, F. Articles by Zhu, C. Search for Related Content PubMed PubMed Citation Articles by Zhang, F. Articles by Zhu, C. Social Bookmarking                      What's this?

Two-dimensional Kinetics Regulation of _L2-ICAM-1 Interaction by Conformational Changes of the _L-Inserted Domain^*

Fang Zhang, Warren D. Marcus1, Nimita H. Goyal¶, Periasamy Selvaraj¶, Timothy A. Springer||, and Cheng Zhu2

From the Coulter Department of Biomedical Engineering and Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, the ^¶Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, and the ^||CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

The leukocyte integrin _L2 mediates cell adhesion and migration during inflammatory and immune responses. Ligand binding of _L2 is regulated by or induces conformational changes in the inserted (I) domain. By using a micropipette, we measured the conformational regulation of two-dimensional (2D) binding affinity and the kinetics of cell-bound intercellular adhesion molecule-1 interacting with _L2 or isolated I domain expressed on K562 cells. Locking the I domain into open and intermediate conformations with a disulfide bond increased the affinities by 8000- and 30-fold, respectively, from the locked closed conformation, which has similar affinity as the wild-type I domain. Most surprisingly, the 2D affinity increases were due mostly to the 2D on-rate increases, as the 2D off-rates only decreased by severalfold. The wild-type _L2, but not its I domain in isolation, could be up-regulated by Mn²⁺ or Mg²⁺ to have high affinities and on-rates. Locking the I domain in any of the three conformations abolished the ability of divalent cations to regulate 2D affinity. These results indicate that a downward displacement of the I domain C-terminal helix, induced by conformational changes of other domains of the _L2, is required for affinity and on-rate up-regulation.

Received for publication, September 22, 2005

^* This work was supported in part by National Institutes of Health Grants AI44902 and AI38282 (to C. Z.), AI049400 (to P. S.), and CA31798 (to T. A. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of a United Negro College Fund-Merck postdoctoral fellowship. Present address: Dept. of Chemical and Materials Engineering, Arizona State University, Tempe, AZ 85287.

² To whom correspondence and reprint requests should be addressed: Wallace H. Coulter Dept. of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0363. Tel.: 404-894-3269; Fax: 404-385-1397; E-mail: cheng.zhu{at}me.gatech.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Kong, A. J. Garcia, A. P. Mould, M. J. Humphries, and C. Zhu Demonstration of catch bonds between an integrin and its ligand J. Cell Biol., June 29, 2009; 185(7): 1275 - 1284. [Abstract] [Full Text] [PDF]

				H. A. Wasserman, C. D. Beal, Y. Zhang, N. Jiang, C. Zhu, and B. D. Evavold MHC Variant Peptide-Mediated Anergy of Encephalitogenic T Cells Requires SHP-1 J. Immunol., November 15, 2008; 181(10): 6843 - 6849. [Abstract] [Full Text] [PDF]

				Q. Shi, Y.-H. Chien, and D. Leckband Biophysical Properties of Cadherin Bonds Do Not Predict Cell Sorting J. Biol. Chem., October 17, 2008; 283(42): 28454 - 28463. [Abstract] [Full Text] [PDF]

				S. Liang, C. Fu, D. Wagner, H. Guo, D. Zhan, C. Dong, and M. Long Two-dimensional kinetics of {beta}2-integrin and ICAM-1 bindings between neutrophils and melanoma cells in a shear flow Am J Physiol Cell Physiol, March 1, 2008; 294(3): C743 - C753. [Abstract] [Full Text] [PDF]

				Y.-H. Chien, N. Jiang, F. Li, F. Zhang, C. Zhu, and D. Leckband Two Stage Cadherin Kinetics Require Multiple Extracellular Domains but Not the Cytoplasmic Region J. Biol. Chem., January 25, 2008; 283(4): 1848 - 1856. [Abstract] [Full Text] [PDF]

				J. Huang, L. J. Edwards, B. D. Evavold, and C. Zhu Kinetics of MHC-CD8 Interaction at the T Cell Membrane J. Immunol., December 1, 2007; 179(11): 7653 - 7662. [Abstract] [Full Text] [PDF]

				V. I. Zarnitsyna, J. Huang, F. Zhang, Y.-H. Chien, D. Leckband, and C. Zhu From the Cover: Memory in receptor-ligand-mediated cell adhesion PNAS, November 13, 2007; 104(46): 18037 - 18042. [Abstract] [Full Text] [PDF]

				P. Li, N. Jiang, S. Nagarajan, R. Wohlhueter, P. Selvaraj, and C. Zhu Affinity and Kinetic Analysis of Fc{gamma} Receptor IIIa (CD16a) Binding to IgG Ligands J. Biol. Chem., March 2, 2007; 282(9): 6210 - 6221. [Abstract] [Full Text] [PDF]

				M. L. Dustin and C. Zhu T cells like a firm molecular handshake PNAS, March 21, 2006; 103(12): 4335 - 4336. [Full Text] [PDF]