The role of the divalent cation in the structure of the I domain from the CD11a/CD18 integrin

Aidong Qu, Daniel J. Leahy

Research output: Contribution to journalArticle

Abstract

Background: The integrin family of cell-surface recaptors mediates a wide variety of cell-cell and cell-extracellular matrix interactions. Integrin-ligand interactions are invariably dependent on the presence of divalent cations, and a subset of integrins contain a ~200 amino acid inserted (I) domain that is important for ligand binding activity and contains a single divalent cation binding site. Many integrins are believed to respond to stimuli by undergoing a conformational change that increases their affinity for ligand, and there is a clear difference between two crystal structures of the CD11bI domain with different divalent cations (magnesium and manganese) bound. In addition to the different bound cation, a 'ligand mimetic' crystal lattice interaction in the CD11b I domain structure with bound magnesium has led to the interpretation that the different CD11b I domain structures represent different affinity states of I domains. The influence of the bound cation on I domain structure and function remains incompletely understood, however. The crystal structure of the CD11a I domain bound to manganese is known. We therefore set out to determine whether this structure changes when the metal ion is altered or removed. Results: We report hera the crystal structures of the CD11a I domain determined in the absence of bound metal ion and with bound magnesium ion. No major structural rearrangements are observed in the metal-binding site of the CD11a I domain in the absence or presence of bound manganese ion. The structures of the CD11a I domain with magnesium or manganese bound are extremely similar. Conclusions: The conformation of the CD11a I domain is not altered by changes in metal ion binding. The cation-dependence of ligand binding thus indicates that the metal ion is either involved in direct interaction with ligand or required to promote a favorable quaternary arrangement of the integrin.

Original languageEnglish (US)
Pages (from-to)931-942
Number of pages12
JournalStructure
Volume4
Issue number8
DOIs
StatePublished - Aug 15 1996

Fingerprint

Divalent Cations
Integrins
Ions
Manganese
Ligands
Metals
Magnesium
Cations
Binding Sites
Extracellular Matrix
Amino Acids

Keywords

  • anomalous diffraction
  • MAD
  • magnesium
  • manganese
  • selenomethionine
  • X-ray

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

The role of the divalent cation in the structure of the I domain from the CD11a/CD18 integrin. / Qu, Aidong; Leahy, Daniel J.

In: Structure, Vol. 4, No. 8, 15.08.1996, p. 931-942.

Research output: Contribution to journalArticle

Qu, Aidong ; Leahy, Daniel J. / The role of the divalent cation in the structure of the I domain from the CD11a/CD18 integrin. In: Structure. 1996 ; Vol. 4, No. 8. pp. 931-942.
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abstract = "Background: The integrin family of cell-surface recaptors mediates a wide variety of cell-cell and cell-extracellular matrix interactions. Integrin-ligand interactions are invariably dependent on the presence of divalent cations, and a subset of integrins contain a ~200 amino acid inserted (I) domain that is important for ligand binding activity and contains a single divalent cation binding site. Many integrins are believed to respond to stimuli by undergoing a conformational change that increases their affinity for ligand, and there is a clear difference between two crystal structures of the CD11bI domain with different divalent cations (magnesium and manganese) bound. In addition to the different bound cation, a 'ligand mimetic' crystal lattice interaction in the CD11b I domain structure with bound magnesium has led to the interpretation that the different CD11b I domain structures represent different affinity states of I domains. The influence of the bound cation on I domain structure and function remains incompletely understood, however. The crystal structure of the CD11a I domain bound to manganese is known. We therefore set out to determine whether this structure changes when the metal ion is altered or removed. Results: We report hera the crystal structures of the CD11a I domain determined in the absence of bound metal ion and with bound magnesium ion. No major structural rearrangements are observed in the metal-binding site of the CD11a I domain in the absence or presence of bound manganese ion. The structures of the CD11a I domain with magnesium or manganese bound are extremely similar. Conclusions: The conformation of the CD11a I domain is not altered by changes in metal ion binding. The cation-dependence of ligand binding thus indicates that the metal ion is either involved in direct interaction with ligand or required to promote a favorable quaternary arrangement of the integrin.",
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KW - anomalous diffraction

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