PDBsum entry 1p53

Cell adhesion

PDB id: 1p53

Contents

Protein chain

250 a.a. *

Ligands

NAG ×6

Waters ×65

* Residue conservation analysis

PDB id:

1p53

Name:

Cell adhesion

Title:

The crystal structure of icam-1 d3-d5 fragment

Structure:

Intercellular adhesion molecule-1. Chain: a, b. Fragment: icam-1 extracellular domain 3-5, ecto-fragment. Synonym: icam-1, major group rhinovirus receptor, cd54 antigen. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: icam1. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho.Lec3.2.8.1.

Resolution:

3.06Å R-factor: 0.220 R-free: 0.252

Authors:

Y.Yang,C.D.Jun,J.H.Liu,R.Zhang,A.Jochimiak,T.A.Springer,J.H.Wang

Key ref:

Y.Yang et al. (2004). Structural basis for dimerization of ICAM-1 on the cell surface. Mol Cell, 14, 269-276. PubMed id: 15099525 DOI: 10.1016/S1097-2765(04)00204-7

Date:

24-Apr-03 Release date: 04-May-04

Protein chains

P05362  (ICAM1_HUMAN) -  Intercellular adhesion molecule 1 from Homo sapiens

Seq: 532 a.a.

Struc: 250 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/S1097-2765(04)00204-7

Mol Cell 14:269-276 (2004)

PubMed id: 15099525

Structural basis for dimerization of ICAM-1 on the cell surface.

Y.Yang, C.D.Jun, J.H.Liu, R.Zhang, A.Joachimiak, T.A.Springer, J.H.Wang.

ABSTRACT

We have determined the 3.0 A crystal structure of the three C-terminal domains 3-5 (D3-D5) of ICAM-1. Combined with the previously known N-terminal two-domain structure (D1D2), a model of an entire ICAM-1 extracellular fragment has been constructed. This model should represent a general architecture of other ICAM family members, particularly ICAM-3 and ICAM-5. The observed intimate dimerization interaction at D4 and a stiff D4-D5 stem-like architecture provide a good structural explanation for the existence of preformed ICAM-1 cis dimers on the cell membrane. Together with another dimerization interface at D1, a band-like one-dimensional linear cluster of ICAM-1 on an antigen-presenting cell (APC) surface can be envisioned, which might explain the formation of an immunological synapse between an activated T cell and APC which is critical for T cell receptor signaling.

Selected figure(s)

Figure 2.
Figure 2. The Sequence Alignment of ICAM-1 with ICAM-3 and ICAM-5As shown in the figure, ICAM-1, ICAM-3, and ICAM-5 align very well. The conserved residues include all cysteines (yellow), three integrin binding residues (cyan), those involved in the D4–D4 dimerization interface (residues forming a salt bridge are in green and hydrophobic contacts are in yellow-green), and those involved in the D3–D4 bending interface (magenta). In this figure, each domain's first residue is manifest with its label, β strands are marked above the ICAM-1 sequence, and every tenth residue is marked with a dot above the ICAM-1 sequence. In addition, glycosylation sites are colored in red, whereas the disordered 16 residues in D4 of the D3–D5 crystal structure are shaded in gray.

Figure 3.
Figure 3. The Molecular Structure of the Entire ICAM-1 Ectofragment and the ICAM-1 Dimer(A) This ICAM-1 D1–D5 model was constructed by linking the known D1D2 structure and the D3–D5 structure reported here at the pivot residue Val186 as described in the Experimental Procedures. Assuming that D5 stands vertically on the cell membrane, both the key α[L]β[2] binding site Glu34 of D1 and the α[M]β[2] binding sites Asp229 and Glu254 of D3 (all shown in ball-and-stick representation) point upward, available for ligand binding from the opposing cell above. Note that the Glu34 is on a relatively flat surface, whereas the Asp229 is on a protruded loop. All seven identified glycans are shown in ball-and-stick representation (prepared with RIBBONS [Carson, 1995]).(B) This is the modeled D2–D3 interface. Domains 2 and 3 are colored in silver and cyan, respectively. Shown here are only the side chains that contribute to the interface. The broken lines depict a salt link between Arg150 of D2 and Asp241 of D3. On the other side of the interface the sugar moiety on D3's Asn269 packs onto the indole ring of D2's Trp97. At the center, two main chain hydrogen bonds are formed between the pivot Val186 and Phe216 in D3's BC loop. Joining them is a group of hydrophobic residues, including the conserved cis-Pro217, that comprise a cushion (Wang and Springer, 1998) (prepared with RIBBONS [Carson, 1995]).(C) In this D3–D5 dimer drawing, one molecule is in cyan and the other in green, while disulfide bonds are in yellow. Glycans are drawn in ball-and-stick representation. The two molecules have their D4s integrated into a “superdomain.” In the inset, extensive hydrophobic contacts in the D4–D4 interface are seen, which include Val301, Val303, Leu329, Leu331, and Phe342 from each molecule. There are also two pairs of charged hydrogen bonds between one molecule's Arg340 and its dyad-mate's Asp337 and vice versa. The view in the inset is flipped 180° vertically for clarity (prepared with RIBBONS [Carson, 1995]).(D) In this drawing, ICAM-1 D1–D5 molecules form D4–D4 dimer, and D4–D4 dimers come together through D1–D1 contacts. The W-shaped tetramers can further propagate into a band-like one-dimensional cluster on the antigen-presenting cell surface. The αLβ2 I domain (magenta) binds to ICAM-1 D1 at the opposite face of D1–D1 dimerization. The glycans on ICAM-1 are in yellow (prepared with RIBBONS [Carson, 1995]).

The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 14, 269-276) copyright 2004.