3BN3

crystal structure of ICAM-5 in complex with aL I domain

Summary for 3BN3

• Entry DOI: 10.2210/pdb3bn3/pdb
• Descriptor: Integrin alpha-L, Intercellular adhesion molecule 5, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: icam-5, i domain, integrin, allosteric mobility, cell adhesion, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 44165.56

Authors

Zhang, H.,Springer, T.A.,Wang, J.-h. (deposition date: 2007-12-13, release date: 2008-08-19, Last modification date: 2024-11-20)

Primary citation

Zhang, H.,Casasnovas, J.M.,Jin, M.,Liu, J.H.,Gahmberg, C.G.,Springer, T.A.,Wang, J.-h.
An unusual allosteric mobility of the C-terminal helix of a high-affinity alpha L integrin I domain variant bound to ICAM-5
Mol.Cell, 31:432-437, 2008

PubMed 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.

PubMed: 18691975
DOI: 10.1016/j.molcel.2008.06.022

Experimental method

X-RAY DIFFRACTION (2.099 Å)