PDBsum entry 1hh9

Immune system/peptide

PDB id: 1hh9

Contents

Protein chains

214 a.a. *

213 a.a. *

12 a.a. *

Waters ×52

* Residue conservation analysis

PDB id:

1hh9

Name:

Immune system/peptide

Title:

Anti-p24 (HIV-1) fab fragment cb41 complexed with a peptide

Structure:

Igg2a kappa antibody cb41 (light chain). Chain: a. Igg2a kappa antibody cb41 (heavy chain). Chain: b. Pep-2. Chain: c. Engineered: yes. Other_details: epitope-related peptide

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/c. Cell_line: cb 4/1/1/f6 b-cell hybridoma. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Biol. unit:

Hetero-Trimer (from PDB file)

Resolution:

2.70Å R-factor: 0.282 R-free: 0.333

Authors:

M.Hahn,H.Wessner,J.Schneider-Mergener,W.Hohne

Key ref:

U.Hoffmüller et al. (2000). Evolutionary transition pathways for changing peptide ligand specificity and structure. EMBO J, 19, 4866-4874. PubMed id: 10990450 DOI: 10.1093/emboj/19.18.4866

Date:

21-Dec-00 Release date: 12-Jan-01

Protein chain

P01837  (IGKC_MOUSE) -  Immunoglobulin kappa constant from Mus musculus

Seq: 107 a.a.

Struc: 214 a.a.*

Protein chain

P01864  (GCAB_MOUSE) -  Ig gamma-2A chain C region secreted form from Mus musculus

Seq: 335 a.a.

Struc: 213 a.a.

Protein chain

No UniProt id for this chain

Struc: 12 a.a.

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

DOI no: 10.1093/emboj/19.18.4866

EMBO J 19:4866-4874 (2000)

PubMed id: 10990450

Evolutionary transition pathways for changing peptide ligand specificity and structure.

U.Hoffmüller, T.Knaute, M.Hahn, W.Höhne, J.Schneider-Mergener, A.Kramer.

ABSTRACT

We identified evolutionary pathways for the inter- conversion of three sequentially and structurally unrelated peptides, GATPEDLNQKL, GLYEWGGARI and FDKEWNLIEQN, binding to the same site of the hypervariable region of the anti-p24 (HIV-1) monoclonal antibody CB4-1. Conversion of these peptides into each other could be achieved in nine or 10 single amino acid substitution steps without loss of antibody binding. Such pathways were identified by analyzing all 7 620 480 pathways connecting 2560 different peptides, and testing them for CB4-1 binding. The binding modes of intermediate peptides of selected optimal pathways were characterized using complete sets of substitution analogs, revealing that a number of sequential substitutions accumulated without changing the pattern of key interacting residues. At a distinct step, however, one single amino acid exchange induces a sudden change in the binding mode, indicating a flip in specificity and conformation. Our data represent a model of how different specificities, structures and functions might evolve in protein-protein recognition.

Selected figure(s)

Figure 4.
Figure 4 Substitutional analyses of peptide intermediates of the three best transition pathways. Complete sets of single substitution analogs of each intermediate were prepared on cellulose membranes and tested for CB4-1 binding. Each position of the peptides was substituted by 20 amino acids (rows). The spots in the first column are identical and correspond to the starting peptides (wt, control). Other spots are single substitution analogs. Binding intensities can only be compared quantitatively within one substitutional analysis due to different incubation reactions and exposure times.

Figure 5.
Figure 5 Complex structure of h-pep and the transition analog DATPEDLGARL. X-ray structures of the peptides GATPEDLNQKL (h-pep, blue) and DATPEDLGARL (h-pep u1-pep intermediate 4, brown) with CB4-1 hypervariable regions (gray). For visualization the program ICM (Figure 1) was used.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 4866-4874) copyright 2000.

Figures were selected by an automated process.