PDBsum entry 4xyn

Membrane protein, metal binding protein

PDB id: 4xyn

Contents

Protein chains

90 a.a.

Ligands

ARG-THR-GLU-ALA-TRP-LYS-VAL-LEU-SER

Metals

_CA ×8

Waters ×35

PDB id:

4xyn

Name:

Membrane protein, metal binding protein

Title:

X-ray structure of ca(2+)-s100b with human rage-derived w61 peptide

Structure:

Receptor for advanced glycation endproducts-derived peptide (w61). Chain: p. Engineered: yes. Protein s100-b. Chain: a, b, c, d. Synonym: s-100 protein beta chain,s-100 protein subunit beta,s100 calcium-binding protein b. Engineered: yes

Source:

Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Homo sapiens. Human. Organism_taxid: 9606. Gene: s100b. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.55Å R-factor: 0.205 R-free: 0.254

Authors:

J.L.Jensen,V.S.K.Indurthi,D.Neau,S.W.Vetter,C.L.Colbert

Key ref:

J.L.Jensen et al. (2015). Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide complex. Acta Crystallogr D Biol Crystallogr, 71, 1176-1183. PubMed id: 25945582 DOI: 10.1107/S1399004715004216

Date:

02-Feb-15 Release date: 13-May-15

Supersedes:

4n6i

Protein chains

P04271  (S100B_HUMAN) -  Protein S100-B from Homo sapiens

Seq: 92 a.a.

Struc: 90 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1107/S1399004715004216

Acta Crystallogr D Biol Crystallogr 71:1176-1183 (2015)

PubMed id: 25945582

Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide complex.

J.L.Jensen, V.S.Indurthi, D.B.Neau, S.W.Vetter, C.L.Colbert.

ABSTRACT

S100B is a damage-associated molecular pattern protein that, when released into the extracellular milieu, triggers initiation of the inflammatory response through the receptor for advanced glycation end products (RAGE). Recognition of S100B is accomplished via the amino-terminal variable immunoglobulin domain (V-domain) of RAGE. To gain insights into this interaction, a complex between S100B and a 15-amino-acid peptide derived from residues 54-68 of the V-domain was crystallized. The X-ray crystal structure was solved to 2.55 Å resolution. There are two dimers of S100B and one peptide in the asymmetric unit. The binding interface of this peptide is compared with that found in the complex between S100B and the 12-amino-acid CapZ-derived peptide TRTK-12. This comparison reveals that although the peptides adopt completely different backbone structures, the residues buried at the interface interact with S100B in similar regions to form stable complexes. The binding affinities of S100B for the intact wild-type V-domain and a W61A V-domain mutant were determined to be 2.7 ± 0.5 and 1.3 ± 0.7 µM, respectively, using fluorescence titration experiments. These observations lead to a model whereby conformational flexibility in the RAGE receptor allows the adoption of a binding conformation for interaction with the stable hydrophobic groove on the surface of S100B.