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

被引:130
作者
Qu, AD [1 ]
Leahy, DJ [1 ]
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT BIOPHYS & BIOPHYS CHEM, BALTIMORE, MD 21205 USA
基金
美国国家卫生研究院;
关键词
anomalous diffraction; MAD; magnesium; manganese; selenomethionine; X-ray;
D O I
10.1016/S0969-2126(96)00100-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: The integrin family of cell-surface receptors 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 similar to 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 CD11b I 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 here 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.
引用
收藏
页码:931 / 942
页数:12
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