Arrangement of domains, and amino acid residues required for binding of vascular cell adhesion molecule-1 to its counter-receptor VLA-4 (alpha 4 beta 1)

doi:10.1083/jcb.124.4.601

This Article

	Full Text (PDF, 2099K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Osborn, L.
	Articles by Kirchhausen, T.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Osborn, L.
	Articles by Kirchhausen, T.


Social Bookmarking

	What's this?

ARTICLES

Arrangement of domains, and amino acid residues required for binding of vascular cell adhesion molecule-1 to its counter-receptor VLA-4 (alpha 4 beta 1)

L Osborn, C Vassallo, BG Browning, R Tizard, DO Haskard, CD Benjamin, I Dougas and T Kirchhausen
Biogen, Inc., Cambridge, Massachusetts 02142.

Interaction of the vascular cell adhesion molecule (VCAM-1) with its counter-receptor very late antigen-4 (VLA-4) (integrin alpha 4 beta 1) is important for a number of developmental pathways and inflammatory functions. We are investigating the molecular mechanism of this binding, in the interest of developing new anti-inflammatory drugs that block it. In a previous report, we showed that the predominant form of VCAM-1 on stimulated endothelial cells, seven-domain VCAM (VCAM-7D), is a functionally bivalent molecule. One binding site requires the first and the other requires the homologous immunoglobulin-like domain. Rotary shadowing and electron microscopy of recombinant soluble VCAM-7D molecules suggests that the seven Ig-like domains are extended in a slightly bent linear array, rather than compactly folded together. We have systematically mutagenized the first domain of VCAM-6D (a monovalent, alternately spliced version mission domain 4) by replacing 3-4 amino acids of the VCAM sequence with corresponding portions of the related ICAM-1 molecule. Specific amino acids, important for binding VLA-4 include aspartate 40 (D40), which corresponds to the acidic ICAM- 1 residue glutamate 34 (E34) previously reported to be essential for binding of ICAM-1 to its integrin counter-receptor LFA-1. A small region of VCAM including D40, QIDS, can be replaced by the similar ICAM- 1 sequence, GIET, without affecting function or epitopes, indicating that this region is part of a general integrin-binding structure rather than a determinant of binding specificity for a particular integrin. The VCAM-1 sequence G65NEH also appears to be involved in binding VLA-4.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

DeNardo, S. J., Liu, R., Albrecht, H., Natarajan, A., Sutcliffe, J. L., Anderson, C., Peng, L., Ferdani, R., Cherry, S. R., Lam, K. S. (2009). 111In-LLP2A-DOTA Polyethylene Glycol-Targeting {alpha}4{beta}1 Integrin: Comparative Pharmacokinetics for Imaging and Therapy of Lymphoid Malignancies. JNM 50: 625-634 [Abstract] [Full Text]
Shinde, A. V., Bystroff, C., Wang, C., Vogelezang, M. G., Vincent, P. A., Hynes, R. O., Van De Water, L. (2008). Identification of the Peptide Sequences within the EIIIA (EDA) Segment of Fibronectin That Mediate Integrin {alpha}9{beta}1-dependent Cellular Activities. J. Biol. Chem. 283: 2858-2870 [Abstract] [Full Text]
Barthel, S. R., Johansson, M. W., McNamee, D. M., Mosher, D. F. (2008). Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma. J. Leukoc. Biol. 83: 1-12 [Abstract] [Full Text]
Sadhu, C., Ting, H. J., Lipsky, B., Hensley, K., Garcia-Martinez, L. F., Simon, S. I., Staunton, D. E. (2007). CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity. J. Leukoc. Biol. 81: 1395-1403 [Abstract] [Full Text]
Barthel, S. R., Annis, D. S., Mosher, D. F., Johansson, M. W. (2006). Differential Engagement of Modules 1 and 4 of Vascular Cell Adhesion Molecule-1 (CD106) by Integrins {alpha}4beta1 (CD49d/29) and {alpha}Mbeta2 (CD11b/18) of Eosinophils. J. Biol. Chem. 281: 32175-32187 [Abstract] [Full Text]
Woodside, D. G., Kram, R. M., Mitchell, J. S., Belsom, T., Billard, M. J., McIntyre, B. W., Vanderslice, P. (2006). Contrasting Roles for Domain 4 of VCAM-1 in the Regulation of Cell Adhesion and Soluble VCAM-1 Binding to Integrin {alpha}4beta1.. J. Immunol. 176: 5041-5049 [Abstract] [Full Text]
Song, G., Yang, Y., Liu, J.-h., Casasnovas, J. M., Shimaoka, M., Springer, T. A., Wang, J.-h. (2005). An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin {alpha}L{beta}2. Proc. Natl. Acad. Sci. USA 102: 3366-3371 [Abstract] [Full Text]
Liu, Y., O'Connor, M. B., Mandell, K. J., Zen, K., Ullrich, A., Buhring, H.-J., Parkos, C. A. (2004). Peptide-Mediated Inhibition of Neutrophil Transmigration by Blocking CD47 Interactions with Signal Regulatory Protein {alpha}. J. Immunol. 172: 2578-2585 [Abstract] [Full Text]
Amersi, F., Shen, X.-D., Moore, C., Melinek, J., Busuttil, R. W., Kupiec-Weglinski, J. W., Coito, A. J. (2003). Fibronectin-{alpha}4{beta}1 Integrin-Mediated Blockade Protects Genetically Fat Zucker Rat Livers from Ischemia/Reperfusion Injury. Am. J. Pathol. 162: 1229-1239 [Abstract] [Full Text]
Liao, Y.-F., Gotwals, P. J., Koteliansky, V. E., Sheppard, D., Van De Water, L. (2002). The EIIIA Segment of Fibronectin Is a Ligand for Integrins alpha 9beta 1 and alpha 4beta 1 Providing a Novel Mechanism for Regulating Cell Adhesion by Alternative Splicing. J. Biol. Chem. 277: 14467-14474 [Abstract] [Full Text]
Zhu, X., Evans, J. P. (2002). Analysis of the Roles of RGD-Binding Integrins, {alpha}4/{alpha}9 Integrins, {alpha}6 Integrins, and CD9 in the Interaction of the Fertilin {beta} (ADAM2) Disintegrin Domain with the Mouse Egg Membrane. Biol. Reprod. 66: 1193-1202 [Abstract] [Full Text]
Taraszka, K. S., Higgins, J. M.G., Tan, K., Mandelbrot, D. A., Wang, J.-h., Brenner, M. B. (2000). Molecular Basis for Leukocyte Integrin {alpha}E{beta}7 Adhesion to Epithelial (E)-Cadherin. JEM 191: 1555-1567 [Abstract] [Full Text]
Sriramarao, P., DiScipio, R. G., Cobb, R. R., Cybulsky, M., Stachnick, G., Castaneda, D., Elices, M., Broide, D. H. (2000). VCAM-1 is more effective than MAdCAM-1 in supporting eosinophil rolling under conditions of shear flow. Blood 95: 592-601 [Abstract] [Full Text]
Rose, D. M., Cardarelli, P. M., Cobb, R. R., Ginsberg, M. H. (2000). Soluble VCAM-1 binding to alpha 4 integrins is cell-type specific and activation dependent and is disrupted during apoptosis in T cells. Blood 95: 602-609 [Abstract] [Full Text]
Abe, Y., Smith, C. W., Katkin, J. P., Thurmon, L. M., Xu, X., Mendoza, L. H., Ballantyne, C. M. (1999). Endothelial {alpha}2,6-Linked Sialic Acid Inhibits VCAM-1- Dependent Adhesion Under Flow Conditions. J. Immunol. 163: 2867-2876 [Abstract] [Full Text]
Van der Vieren, M., Crowe, D. T., Hoekstra, D., Vazeux, R., Hoffman, P. A., Grayson, M. H., Bochner, B. S., Gallatin, W. M., Staunton, D. E. (1999). The Leukocyte Integrin {alpha}D{beta}2 Binds VCAM-1: Evidence for a Binding Interface Between I Domain and VCAM-1. J. Immunol. 163: 1984-1990 [Abstract] [Full Text]
Patel, K. D. (1999). Mechanisms of Selective Leukocyte Recruitment from Whole Blood on Cytokine-Activated Endothelial Cells Under Flow Conditions. J. Immunol. 162: 6209-6216 [Abstract] [Full Text]
Shih, P. T., Brennan, M.-L., Vora, D. K., Territo, M. C., Strahl, D., Elices, M. J., Lusis, A. J., Berliner, J. A. (1999). Blocking Very Late Antigen-4 Integrin Decreases Leukocyte Entry and Fatty Streak Formation in Mice Fed an Atherogenic Diet. Circ. Res. 84: 345-351 [Abstract] [Full Text]
Weber, C., Springer, T. A. (1998). Interaction of Very Late Antigen-4 with VCAM-1 Supports Transendothelial Chemotaxis of Monocytes by Facilitating Lateral Migration. J. Immunol. 161: 6825-6834 [Abstract] [Full Text]
Bell, E. D., May, A. P., Simmons, D. L. (1998). The Leukocyte Function-Associated Antigen-1 (LFA-1)-Binding Site on ICAM-3 Comprises Residues on Both Faces of the First Immunoglobulin Domain. J. Immunol. 161: 1363-1370 [Abstract] [Full Text]
Yokosaki, Y., Matsuura, N., Higashiyama, S., Murakami, I., Obara, M., Yamakido, M., Shigeto, N., Chen, J., Sheppard, D. (1998). Identification of the Ligand Binding Site for the Integrin alpha 9beta 1 in the Third Fibronectin Type III Repeat of Tenascin-C. J. Biol. Chem. 273: 11423-11428 [Abstract] [Full Text]
Newham, P., Craig, S. E., Clark, K., Mould, A. P., Humphries, M. J. (1998). Analysis of Ligand-Induced and Ligand-Attenuated Epitopes on the Leukocyte Integrin {alpha}4{beta}1: VCAM-1, Mucosal Addressin Cell Adhesion Molecule-1, and Fibronectin Induce Distinct Conformational Changes. J. Immunol. 160: 4508-4517 [Abstract] [Full Text]
Zeller, Y., Lohr, J., Sammar, M., Butcher, E. C., Altevogt, P. (1998). Asp-698 and Asp-811 of the Integrin alpha 4-Subunit Are Critical for the Formation of a Functional Heterodimer. J. Biol. Chem. 273: 6786-6795 [Abstract] [Full Text]
Stanley, P., Hogg, N. (1998). The I Domain of Integrin LFA-1 Interacts with ICAM-1 Domain 1�at Residue Glu-34 but Not Gln-73. J. Biol. Chem. 273: 3358-3362 [Abstract] [Full Text]
Higgins, J. M.G., Mandlebrot, D. A., Shaw, S. K., Russell, G. J., Murphy, E. A., Chen, Y.-T., Nelson, W. J., Parker, C. M., Brenner, M. B. (1998). Direct and Regulated Interaction of Integrin {alpha}E{beta}7 with E-Cadherin. JCB 140: 197-210 [Abstract] [Full Text]
Bayless, K., Meininger, G., Scholtz, J., Davis, G. (1998). Osteopontin is a ligand for the alpha4beta1 integrin. J. Cell Sci. 111: 1165-1174 [Abstract]
Tselepis, V. H., Green, L. J., Humphries, M. J. (1997). An RGD to LDV Motif Conversion within the Disintegrin Kistrin Generates an Integrin Antagonist That Retains Potency but Exhibits Altered Receptor Specificity. EVIDENCE FOR A FUNCTIONAL EQUIVALENCE OF ACIDIC INTEGRIN-BINDING MOTIFS. J. Biol. Chem. 272: 21341-21348 [Abstract] [Full Text]
Newham, P., Craig, S. E., Seddon, G. N., Schofield, N. R., Rees, A., Edwards, R. M., Jones, E. Y., Humphries, M. J. (1997). alpha 4 Integrin Binding Interfaces on VCAM-1 and MAdCAM-1. INTEGRIN BINDING FOOTPRINTS IDENTIFY ACCESSORY BINDING SITES THAT PLAY A ROLE IN INTEGRIN SPECIFICITY. J. Biol. Chem. 272: 19429-19440 [Abstract] [Full Text]
Mizuno, T., Yoshihara, Y., Inazawa, J., Kagamiyama, H., Mori, K. (1997). cDNA Cloning and Chromosomal Localization of the Human Telencephalin and Its Distinctive Interaction with Lymphocyte Function-associated Antigen-1. J. Biol. Chem. 272: 1156-1163 [Abstract] [Full Text]
KHAN, U., EDWARDS, J. C. W., McGROUTHER, D. A. (1996). Patterns of Cellular Activation after Tendon Injury. J Hand Surg Eur Vol 21: 813-820 [Abstract]
Karecla, P. I., Green, S. J., Bowden, S. J., Coadwell, J., Kilshaw, PeterJ. (1996). Identification of a Binding Site for Integrin alpha Ebeta 7 in the N-terminal Domain of E-cadherin. J. Biol. Chem. 271: 30909-30915 [Abstract] [Full Text]
Sun, Q.-H., DeLisser, H. M., Zukowski, M. M., Paddock, C., Albelda, S. M., Newman, P. J. (1996). Individually Distinct Ig Homology Domains in PECAM-1 Regulate Homophilic Binding and Modulate Receptor Affinity. J. Biol. Chem. 271: 11090-11098 [Abstract] [Full Text]
Kilger, G., Needham, L. A., Nielsen, P. J., Clements, J., Vestweber, D., Holzmann, B. (1995). Differential Regulation of alpha(4) Integrin-dependent Binding to Domains 1 and 4 of Vascular Cell Adhesion Molecule-1. J. Biol. Chem. 270: 5979-5984 [Abstract] [Full Text]
Holness, C. L., Bates, P. A., Littler, A. J., Buckley, C. D., McDowall, A., Bossy, D., Hogg, N., Simmons, D. L. (1995). Analysis of the Binding Site on Intercellular Adhesion Molecule 3 for the Leukocyte Integrin Lymphocyte Function-associated Antigen 1. J. Biol. Chem. 270: 877-884 [Abstract] [Full Text]
Clements, J., Newham, P, Shepherd, M, Gilbert, R, Dudgeon, T., Needham, L., Edwards, R., Berry, L, Brass, A, Humphries, M. (1994). Identification of a key integrin-binding sequence in VCAM-1 homologous to the LDV active site in fibronectin. J. Cell Sci. 107: 2127-2135 [Abstract]
Bayless, K. J., Davis, G. E. (2001). Identification of Dual alpha 4beta 1 Integrin Binding Sites within a 38 Amino Acid Domain in the N-terminal Thrombin Fragment of Human Osteopontin. J. Biol. Chem. 276: 13483-13489 [Abstract] [Full Text]
Bridges, L. C., Tani, P. H., Hanson, K. R., Roberts, C. M., Judkins, M. B., Bowditch, R. D. (2002). The Lymphocyte Metalloprotease MDC-L (ADAM 28) Is a Ligand for the Integrin alpha 4beta 1. J. Biol. Chem. 277: 3784-3792 [Abstract] [Full Text]