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Literature DB >> 11226249

An isolated, surface-expressed I domain of the integrin alphaLbeta2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond.

C Lu¹, M Shimaoka, M Ferzly, C Oxvig, J Takagi, T A Springer.

Abstract

We introduced disulfide bonds to lock the integrin alphaLbeta2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing alphaLbeta2 heterodimers containing locked-open but not locked-closed or wild-type I domains constitutively adhered to intercellular adhesion molecule-1 (ICAM-1) substrates. Locking the I domain closed abolished constitutive and activatable adhesion. The isolated locked-open I domain bound as well as the activated alphaLbeta2 heterodimer, and binding was abolished by reduction of the disulfide. Lovastatin, which binds under the conformationally mobile C-terminal alpha-helix of the I domain, inhibited binding to ICAM-1 by alphaLbeta2 with wild-type, but not locked-open I domains. These data establish the importance of conformational change in the alphaL I domain for adhesive function and show that this domain is sufficient for full adhesive activity.

Entities: Chemical Gene

Mesh：

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Year: 2001 PMID： 11226249 PMCID： PMC30148 DOI： 10.1073/pnas.041606398

Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205

40 in total

1. Structural and functional studies with antibodies to the integrin beta 2 subunit. A model for the I-like domain.

Authors: C Huang; Q Zang; J Takagi; T A Springer
Journal: J Biol Chem Date: 2000-07-14 Impact factor: 5.157

Review 2. Integrin structure.

Authors: M J Humphries
Journal: Biochem Soc Trans Date: 2000 Impact factor: 5.407

3. Conformational changes in tertiary structure near the ligand binding site of an integrin I domain.

Authors: C Oxvig; C Lu; T A Springer
Journal: Proc Natl Acad Sci U S A Date: 1999-03-02 Impact factor: 11.205

4. The alpha subunit cytoplasmic domain regulates the assembly and adhesiveness of integrin lymphocyte function-associated antigen-1.

Authors: C F Lu; T A Springer
Journal: J Immunol Date: 1997-07-01 Impact factor: 5.422

Review 5. Are changes in integrin affinity and conformation overemphasized?

Authors: G Bazzoni; M E Hemler
Journal: Trends Biochem Sci Date: 1998-01 Impact factor: 13.807

Review 6. The dynamic regulation of integrin adhesiveness.

Authors: M S Diamond; T A Springer
Journal: Curr Biol Date: 1994-06-01 Impact factor: 10.834

7. Cutting edge: a small molecule antagonist of LFA-1-mediated cell adhesion.

Authors: T A Kelly; D D Jeanfavre; D W McNeil; J R Woska; P L Reilly; E A Mainolfi; K M Kishimoto; G H Nabozny; R Zinter; B J Bormann; R Rothlein
Journal: J Immunol Date: 1999-11-15 Impact factor: 5.422

8. Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin.

Authors: A Qu; D J Leahy
Journal: Proc Natl Acad Sci U S A Date: 1995-10-24 Impact factor: 11.205

9. A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1).

Authors: C Huang; T A Springer
Journal: J Biol Chem Date: 1995-08-11 Impact factor: 5.157

10. The lymphocyte function-associated antigen 1 I domain is a transient binding module for intercellular adhesion molecule (ICAM)-1 and ICAM-3 in hydrodynamic flow.

Authors: R Knorr; M L Dustin
Journal: J Exp Med Date: 1997-08-29 Impact factor: 14.307

47 in total

1. Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains.

Authors: C Lu; M Shimaoka; Q Zang; J Takagi; T A Springer
Journal: Proc Natl Acad Sci U S A Date: 2001-02-27 Impact factor: 11.205

2. Stabilizing the integrin alpha M inserted domain in alternative conformations with a range of engineered disulfide bonds.

Authors: Motomu Shimaoka; Chafen Lu; Azucena Salas; Tsan Xiao; Junichi Takagi; Timothy A Springer
Journal: Proc Natl Acad Sci U S A Date: 2002-12-04 Impact factor: 11.205

3. Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo.

Authors: M Shimaoka; C Lu; R T Palframan; U H von Andrian; A McCormack; J Takagi; T A Springer
Journal: Proc Natl Acad Sci U S A Date: 2001-05-15 Impact factor: 11.205

An isolated, surface-expressed I domain of the integrin alphaLbeta2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond.

1. Structural and functional studies with antibodies to the integrin beta 2 subunit. A model for the I-like domain.

Review 2. Integrin structure.

3. Conformational changes in tertiary structure near the ligand binding site of an integrin I domain.

4. The alpha subunit cytoplasmic domain regulates the assembly and adhesiveness of integrin lymphocyte function-associated antigen-1.

Review 5. Are changes in integrin affinity and conformation overemphasized?

Review 6. The dynamic regulation of integrin adhesiveness.

7. Cutting edge: a small molecule antagonist of LFA-1-mediated cell adhesion.

8. Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin.

9. A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1).

10. The lymphocyte function-associated antigen 1 I domain is a transient binding module for intercellular adhesion molecule (ICAM)-1 and ICAM-3 in hydrodynamic flow.

1. Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains.

2. Stabilizing the integrin alpha M inserted domain in alternative conformations with a range of engineered disulfide bonds.

3. Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo.

4. Structure and allosteric regulation of the alpha X beta 2 integrin I domain.

5. Identification of integrin beta subunit mutations that alter heterodimer function in situ.

6. Activation of integrin beta-subunit I-like domains by one-turn C-terminal alpha-helix deletions.

7. Intersubunit signal transmission in integrins by a receptor-like interaction with a pull spring.

8. The C-terminal αI domain linker as a critical structural element in the conformational activation of αI integrins.

9. The αE(CD103)β7 integrin interacts with oral and skin keratinocytes in an E-cadherin-independent manner*.

10. I-domain of lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow.