PDBsum entry 2bjm

Immune system

PDB id: 2bjm

Contents

Protein chains

120 a.a. *

110 a.a. *

Ligands

ANF

* Residue conservation analysis

PDB id:

2bjm

Name:

Immune system

Title:

Spe7:anthrone complex

Structure:

Ige spe7 heavy chain. Chain: h. Fragment: heavy chain, residues 1-120. Engineered: yes. Other_details: anthrone attached. Ige spe7 light chain. Chain: l. Fragment: light chain, residues 1-110. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Biol. unit:

Octamer (from PDB file)

Resolution:

2.15Å R-factor: 0.269 R-free: 0.286

Authors:

L.C.James,D.S.Tawfik

Key ref:

L.C.James and D.S.Tawfik (2005). Structure and kinetics of a transient antibody binding intermediate reveal a kinetic discrimination mechanism in antigen recognition. Proc Natl Acad Sci U S A, 102, 12730-12735. PubMed id: 16129832 DOI: 10.1073/pnas.0500909102

Date:

04-Feb-05 Release date: 18-Aug-05

Protein chain

No UniProt id for this chain

Struc: 120 a.a.

Protein chain

P01724  (LV1B_MOUSE) -  Ig lambda-1 chain V regions MOPC 104E/RPC20/J558/S104 from Mus musculus

Seq: 129 a.a.

Struc: 110 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1073/pnas.0500909102

Proc Natl Acad Sci U S A 102:12730-12735 (2005)

PubMed id: 16129832

Structure and kinetics of a transient antibody binding intermediate reveal a kinetic discrimination mechanism in antigen recognition.

L.C.James, D.S.Tawfik.

ABSTRACT

Induced fit is a predominant phenomenon in protein-ligand interactions, yet it is invariably attributed without establishing the existence, let alone the structure, of the initial, low-affinity encounter complex. We determined the crystal structure of the encounter complex on the pathway of ligand binding by IgE antibody SPE7. We show that this complex is formed by a wide range of ligands that initially bind with identical affinity. Nonspecific ligands rapidly dissociate, whereupon the antibody isomerizes to a nonbinding isomer. Specific ligand complexes, however, slowly isomerize to give a high-affinity complex. This isomerization involves backbone and side-chain rearrangements of up to 14 A and the formation of specific hydrogen bonds. The postbinding conformational switch, combined with the prebinding isomerization to an energetically favorable nonbinding isomer, results in a "kinetic discrimination" mechanism that mediates selective binding, by a factor of >10(3), between highly related ligands that initially bind with the same affinity. This model may apply to proteins that bind multiple ligands in a specific manner or other proteins that, although capable of binding many ligands, are activated by only a few.

Selected figure(s)

Figure 3.
Fig. 3. The binding-site conformations of SPE7. The semitransparent surface view is colored by electrostatic potential (blue for positive, red for negative). Noted are light-chain (L) and heavy-chain (H) CDR3 loops and residues that play a key role in ligand binding. The free antibody isomer Ab^2 1OCW (7) forms a nonspecific encounter complex with a range of ligands, as can be seen in the Ab^2·anthrone structure 1BJM. The latter isomerizes to give the final, high-affinity complex Ab^3·alizarin red 1OAR (see also Movie 3). The ligands stacks against L3 residue Trp-93 in both the Ab^2 and Ab^3 complexes, but anthrone makes no hydrogen bonds with Ab^2. In contrast, alizarin red makes a number of hydrogen bonds to Ab^3.

Figure 4.
Fig. 4. Superposition of H3 loops at different stages of ligand complexation. Shown are CDR loops and side chains for Ab^2 (gray), Ab^2·anthrone (green), and Ab^3·alizarin red (yellow). Although the Ab^2 and Ab^2·anthrone structures vary only slightly (Movie 1), the formation of the final high-affinity complex (Ab^3·alizarin red) is accompanied by significant conformational change, in particular of the H3 loop (Movie 3).

Figures were selected by an automated process.