PDBsum entry 1mq9

Immune system

PDB id: 1mq9

Contents

Protein chain

173 a.a. *

Metals

_MN

Waters ×90

* Residue conservation analysis

PDB id:

1mq9

Name:

Immune system

Title:

Crystal structure of high affinity alphal i domain with ligand mimetic crystal contact

Structure:

Integrin alpha-l. Chain: a. Fragment: integrin alphal i domain. Synonym: leukocyte adhesion glycoprotein lfa-1 alpha chain. Leukocyte function associated molecule 1, alpha chain. Cd11a. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lfa-1 (alphalbeta2). Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.00Å R-factor: 0.212 R-free: 0.265

Authors:

M.Shimaoka,T.Xiao,J.-H.Liu,Y.Yang,Y.Dong,C.-D.Jun,A.Mccormack, R.Zhang,A.Joachimiak,J.Takagi,J.-H.Wang,T.A.Springer

Key ref:

M.Shimaoka et al. (2003). Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell, 112, 99. PubMed id: 12526797 DOI: 10.1016/S0092-8674(02)01257-6

Date:

15-Sep-02 Release date: 14-Jan-03

Protein chain

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

Seq: 1170 a.a.

Struc: 173 a.a.*

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

DOI no: 10.1016/S0092-8674(02)01257-6

Cell 112:99 (2003)

PubMed id: 12526797

Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation.

M.Shimaoka, T.Xiao, J.H.Liu, Y.Yang, Y.Dong, C.D.Jun, A.McCormack, R.Zhang, A.Joachimiak, J.Takagi, J.H.Wang, T.A.Springer.

ABSTRACT

The structure of the I domain of integrin alpha L beta 2 bound to the Ig superfamily ligand ICAM-1 reveals the open ligand binding conformation and the first example of an integrin-IgSF interface. The I domain Mg2+ directly coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241 enables a critical salt bridge. Liganded and unliganded structures for both high- and intermediate-affinity mutant I domains reveal that ligand binding can induce conformational change in the alpha L I domain and that allosteric signals can convert the closed conformation to intermediate or open conformations without ligand binding. Pulling down on the C-terminal alpha 7 helix with introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity.

Selected figure(s)

Figure 1.
Figure 1. Two αL I Domains Bound to an ICAM-1 Dimer(A) Ribbon diagram of one monomeric unit of the intermediate-affinity αL I domain (gold) complex with ICAM-1 domains 1-2 (cyan). The Mg^2+ ion is shown as a magenta sphere. I domain MIDAS and ICAM-1 Glu-34 side chains are shown as ball-and-stick with red oxygen atoms. The interacting β strands C, D, and F of ICAM-1 are labeled. N-acetyl glucosamine residues of ICAM-1 are shown with silver bonds.(B) The two ICAM-1-I domain complexes in the crystallographic asymmetric unit are shown with the I domains colored gold and the two ICAM-1 molecules colored cyan and green. The 2-fold axis between the ICAM-1 molecules is in the vertical direction, normal to the predicted membrane plane. Positions of the magnesium ions (magenta spheres) and Glu-34 of ICAM-1 (CPK) are shown for reference. The ICAM-1 Val-51 residues at the center of the ICAM-1 dimer interface are shown as gray CPK models.(C) A view of domains 1 of the ICAM-1 dimer (cyan and green), rotated about 90° from the view in (B), with domain 1 of the uncomplexed ICAM-1 molecule A dimer (Casasnovas et al., 1998) superimposed using domain 1 of one of the ICAM-1 molecules (black), whereas the other one is colored gray. Figures 1–5 are prepared with programs GLR (provided by L. Esser), Molscript (Kraulis, 1991), Bobscript (Esnouf, 1997), Raster3D (Merritt and Murphy, 1994), GRASP (Nicholls et al., 1991), and Povray (The Povray Team, http://www.povray.org).

Figure 3.
Figure 3. MIDAS StructuresStructures are from the I domain:ICAM-1 complex (A), the pseudo-liganded high-affinity I domain (B), the unliganded high-affinity I domain (C), the unliganded intermediate-affinity I domain (D), and the wild-type I domain (E) (1LFA) (Qu and Leahy, 1996). The keys to the color scheme are shown below, with the ICAM-1 or ligand mimetic molecule colored cyan in (A) and (B). The metal ions are colored blue, water molecule and ligating side chain oxygen atoms are colored red, and the chloride ion from the wild-type I domain structure is colored orange. The MIDAS residues and Glu-34 from ICAM-1 in (A) and Glu-272 from a lattice mate I domain in (B) are shown as ball-and-stick models. Metal coordination and hydrogen bonds are represented by solid black lines and gray dotted lines, respectively.

The above figures are reprinted by permission from Cell Press: Cell (2003, 112, 99-0) copyright 2003.

Figures were selected by an automated process.