PDBsum entry 3fso

Cell adhesion

PDB id: 3fso

Contents

Protein chains

109 a.a. *

113 a.a. *

Waters ×308

* Residue conservation analysis

PDB id:

3fso

Name:

Cell adhesion

Title:

Crystal structure of the calx-beta domain of integrin beta4, calcium soak

Structure:

Integrin beta-4. Chain: a, b. Fragment: calx-beta domain, residues 989-1107. Synonym: gp150. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: itgb4. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.41Å R-factor: 0.184 R-free: 0.212

Authors:

N.Alonso-Garcia,A.Ingles-Prieto,J.M.De Pereda

Key ref:

N.Alonso-García et al. (2009). Structure of the Calx-beta domain of the integrin beta4 subunit: insights into function and cation-independent stability. Acta Crystallogr D Biol Crystallogr, 65, 858-871. PubMed id: 19622870 DOI: 10.1107/S0907444909018745

Date:

11-Jan-09 Release date: 23-Jun-09

Protein chain

P16144  (ITB4_HUMAN) -  Integrin beta-4 from Homo sapiens

Seq: 1822 a.a.

Struc: 109 a.a.*

Protein chain

P16144  (ITB4_HUMAN) -  Integrin beta-4 from Homo sapiens

Seq: 1822 a.a.

Struc: 113 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1107/S0907444909018745

Acta Crystallogr D Biol Crystallogr 65:858-871 (2009)

PubMed id: 19622870

Structure of the Calx-beta domain of the integrin beta4 subunit: insights into function and cation-independent stability.

N.Alonso-García, A.Inglés-Prieto, A.Sonnenberg, J.M.de Pereda.

ABSTRACT

The integrin alpha6beta4 is a receptor for laminins and provides stable adhesion of epithelial cells to the basement membranes. In addition, alpha6beta4 is important for keratinocyte migration during wound healing and favours the invasion of carcinomas into surrounding tissue. The cytoplasmic domain of the beta4 subunit is responsible for most of the intracellular interactions of the integrin; it contains four fibronectin type III domains and a Calx-beta motif. The crystal structure of the Calx-beta domain of beta4 was determined to 1.48 A resolution. The structure does not contain cations and biophysical data support the supposition that the Calx-beta domain of beta4 does not bind calcium. Comparison of the Calx-beta domain of beta4 with the calcium-binding domains of Na(+)/Ca(2+)-exchanger 1 reveals that in beta4 Arg1003 occupies a position equivalent to that of the calcium ions in the Na(+)/Ca(2+)-exchanger. By combining mutagenesis and thermally induced unfolding, it is shown that Arg1003 contributes to the stability of the Calx-beta domain. The structure of the Calx-beta domain is discussed in the context of the function and intracellular interactions of the integrin beta4 subunit and a putative functional site is proposed.

Selected figure(s)

Figure 3.
Figure 3 Structure of the BC, DE and FG loops of 4. (a) Close-up view of the BC (yellow) and DE (pink) loops; the side chain of R1014 plays a central role in the stabilization of this region by establishing hydrogen bonds within the BC loop and with the backbone of the DE loop. D990 in the N-terminus (grey) makes a hydrogen bond to the backbone of the BC loop. (b) Detailed view of the -hairpin at the FG loop. The relative position of the residues that form the type I' -turn (1087-1090) is shown in parentheses. Hydrogen bonds are shown as dashed lines.

Figure 5.
Figure 5 Stereo representations of simulated-annealing OMIT maps of the pseudo-Ca^2+-binding sites of the 4 structures. (a) Structure of molecule A of the asymmetric unit of the native crystal. (b) Structure of molecule B of the asymmetric unit of the native crystal. (c) and (d) show the structures of molecule A and molecule B crystallized in the presence of 2 mM Ca^2+, respectively. Each map (2mF[obs] - DF[calc], contoured at 1 ) was calculated after performing a round of refinement using simulated annealing (initial temperature 5000 K) of models from which the regions shown in the figure were removed. No significant differences were observed in the protein and solvent network between the equivalent molecules of the native and Ca^2+-cocrystallized structures.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2009, 65, 858-871) copyright 2009.

Figures were selected by an automated process.