PDBsum entry 3bn3

Cell adhesion, immune system

PDB id: 3bn3

Contents

Protein chains

180 a.a. *

196 a.a. *

Ligands

NAG-NAG

NAG ×4

GOL ×2

Metals

_MG

Waters ×226

* Residue conservation analysis

PDB id:

3bn3

Name:

Cell adhesion, immune system

Title:

Crystal structure of icam-5 in complex with al i domain

Structure:

Integrin alpha-l. Chain: a. Fragment: i domain. Synonym: leukocyte adhesion glycoprotein lfa-1 alpha chain. Lfa-1a. Leukocyte function-associated molecule 1 alpha chain. Cd11a antigen. Engineered: yes. Mutation: yes. Intercellular adhesion molecule 5. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: itgal, cd11a. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: icam5, tlcn, tln. Expressed in: cricetulus griseus. Expression_system_taxid: 10029.

Resolution:

2.10Å R-factor: 0.193 R-free: 0.235

Authors:

H.Zhang,T.A.Springer,J.-H.Wang

Key ref:

H.Zhang et al. (2008). An unusual allosteric mobility of the c-terminal helix of a high-affinity alphaL integrin I domain variant bound to ICAM-5. Mol Cell, 31, 432-437. PubMed id: 18691975 DOI: 10.1016/j.molcel.2008.06.022

Date:

13-Dec-07 Release date: 19-Aug-08

Protein chain

P20701  (ITAL_HUMAN) -  Integrin alpha-L from Homo sapiens

Seq: 1170 a.a.

Struc: 180 a.a.*

Protein chain

Q9UMF0  (ICAM5_HUMAN) -  Intercellular adhesion molecule 5 from Homo sapiens

Seq: 924 a.a.

Struc: 196 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1016/j.molcel.2008.06.022

Mol Cell 31:432-437 (2008)

PubMed id: 18691975

An unusual allosteric mobility of the c-terminal helix of a high-affinity alphaL integrin I domain variant bound to ICAM-5.

H.Zhang, J.M.Casasnovas, M.Jin, J.H.Liu, C.G.Gahmberg, T.A.Springer, J.H.Wang.

ABSTRACT

Integrins are cell surface receptors that transduce signals bidirectionally across the plasma membrane. The key event of integrin signaling is the allosteric regulation between its ligand-binding site and the C-terminal helix (alpha7) of integrin's inserted (I) domain. A significant axial movement of the alpha7 helix is associated with the open, active conformation of integrins. We describe the crystal structure of an engineered high-affinity I domain from the integrin alpha(L)beta(2) (LFA-1) alpha subunit in complex with the N-terminal two domains of ICAM-5, an adhesion molecule expressed in telencephalic neurons. The finding that the alpha7 helix swings out and inserts into a neighboring I domain in an upside-down orientation in the crystals implies an intrinsically unusual mobility of this helix. This remarkable feature allows the alpha7 helix to trigger integrin's large-scale conformational changes with little energy penalty. It serves as a mechanistic example of how a weakly bound adhesion molecule works in signaling.

Selected figure(s)

Figure 1.
Figure 1. Ribbon Diagram of the ICAM-5/dm-I Complex
Two symmetry-related complexes of the ICAM-5/dm-I domain are shown. In one complex ICAM-5 is in cyan and the I domain in green. In the other complex the I domain is in magenta and the ICAM-5 molecule is in shadow for clarity. The C-terminal α7 helix of the magenta I domain inserts into a groove in the green I domain in an upside-down fashion. Glu-37 in ICAM-5 D1 that binds to the I domain's MIDAS is shown in red as a ball-and-stick model. The figures are all prepared with Pymol (http://www.pymol.org/).

Figure 2.
Figure 2. Superimposition of the ICAM-3/HA Complex onto the ICAM-5/dm-I Complex
ICAM-3/HA is in red and the ICAM-5/dm-I complex is in cyan. For clarity, the ICAM-5 D2 is not shown in the figures. The conserved Glu-37 is in yellow.
(A) The superposition is based on I domains. Side chains at the two mutation sites are shown in a ball-and-stick model with Phe265 and Phe292 in the HA replaced by Ser265 and Gly292 in the dm-I domain, respectively. Also shown are Leu289s where the polypeptide chains of the two I domains start to run opposite directions.
(B) The ICAMs' domain D1s were used for superposition. HA I domain from the ICAM-3/HA complex is not shown for clarity. The loops of R41-T45 in ICAM-5 and S41-V45 in ICAM-3 are colored green and magenta, respectively. Residue N43 and attached sugar NAG-2 from ICAM-5 D1 are also shown as a ball-and-stick model.
(C) The stereo view of the local region around MIDAS of superimposed I domains. The I domain from ICAM-5 complex is in green, that from the ICAM-3 complex is in cyan, and the closed form of the α[L] I domain (1ZOP) in magenta. Glu-37 from ICAM-5 that binds to MIDAS is shown in yellow. The metal ion is shown as a ball. Side chains of residues D239, S265, F265, and G262 are labeled and shown in a ball-and-stick model. The yellow arrows indicate the movement direction of the β4α5 loop and the F265 ring from closed form to open form.

The above figures are reprinted from an Open Access publication published by Cell Press: Mol Cell (2008, 31, 432-437) copyright 2008.

Figures were selected by the author.