PDBsum entry 1idn

Cell adhesion

PDB id: 1idn

Contents

Protein chain

190 a.a. *

Waters ×178

* Residue conservation analysis

PDB id:

1idn

Name:

Cell adhesion

Title:

Mac-1 i domain metal free

Structure:

Cd11b. Chain: 1, 2. Fragment: mac-1 alpha domain. Synonym: cell surface glycoprotein mac-1 alpha subunit. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.70Å R-factor: 0.174

Authors:

E.T.Baldwin

Key ref:

E.T.Baldwin et al. (1998). Cation binding to the integrin CD11b I domain and activation model assessment. Structure, 6, 923-935. PubMed id: 9687375 DOI: 10.1016/S0969-2126(98)00093-8

Date:

10-Jun-98 Release date: 04-Nov-98

Protein chains

P11215  (ITAM_HUMAN) -  Integrin alpha-M from Homo sapiens

Seq: 1152 a.a.

Struc: 189 a.a.

DOI no: 10.1016/S0969-2126(98)00093-8

Structure 6:923-935 (1998)

PubMed id: 9687375

Cation binding to the integrin CD11b I domain and activation model assessment.

E.T.Baldwin, R.W.Sarver, G.L.Bryant, K.A.Curry, M.B.Fairbanks, B.C.Finzel, R.L.Garlick, R.L.Heinrikson, N.C.Horton, L.L.Kelley, A.M.Mildner, J.B.Moon, J.E.Mott, V.T.Mutchler, C.S.Tomich, K.D.Watenpaugh, V.H.Wiley.

ABSTRACT

BACKGROUND: The integrin family of cell-surface receptors mediate cell adhesion through interactions with the extracellular matrix or other cell-surface receptors. The alpha chain of some integrin heterodimers includes an inserted 'I domain' of about 200 amino acids which binds divalent metal ions and is essential for integrin function. Lee et al. proposed that the I domain of the integrin CD11b adopts a unique 'active' conformation when bound to its counter receptor. In addition, they proposed that the lack of adhesion in the presence of Ca2+ ion reflected the stabilization of an 'inactive' I-domain conformation. We set out to independently determine the structure of the CD11 b I domain and to evaluate the structural effects of divalent ion binding to this protein. RESULTS: We have determined the X-ray structure of a new crystal form of the CD11 b I domain in the absence of added metal ions by multiple isomorphous replacement (MIR). Metal ions were easily introduced into this crystal form allowing the straight-forward assessment of the structural effects of divalent cation binding at the metal ion dependent adhesion site (MIDAS). The equilibrium binding constants for these ions were determined by titration calorimetry. The overall protein conformation and metal-ion coordination of the I domain is the same as that observed for all previously reported CD11 a I-domain structures and a CD11 b I-domain complex with Mn2+. These structures define a majority conformation. CONCLUSIONS: Addition of the cations Mg2+, Mn2+ and Cd2+ to the metal-free I domain does not induce conformational changes in the crystalline environment. Moreover, we find that Ca2+ binds poorly to the I domain which serves to explain its failure to support adhesion. We show that the active conformation proposed by Lee et al, is likely to be a construct artifact and we propose that the currently available data do not support a dramatic structural transition for the I domain during counter-receptor binding.

Selected figure(s)

Figure 1.
Figure 1. I domain secondary structure and conformational comparison. (a) Ribbon diagram of the CD11b I domain with Mg2+ ion bound at the C-terminal end of the mostly parallel b sheet (green). The seven a helices are shown in red. The Mg2+ ion (pink sphere) is coordinated by the conserved residues Ser142, Ser144 and Asp242, which are shown in ball-and-stick representation. (b) Superimposed ribbon diagrams of the majority conformation of the CD11b I domain (red) and the 1ido crystal structure (green). The different positions of Phe275 and Phe302 (ball-and-stick representation) are indicated. The Mg2+ ions are indicated by the pink and green spheres. (The figures were prepared using MOLSCRIPT [82] and rendered using RASTER3D [83].)

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 923-935) copyright 1998.

Figure was selected by an automated process.