PDBsum entry 2mjw

Signaling protein/metal binding protein

PDB id: 2mjw

Contents

Protein chains

101 a.a.

94 a.a.

PDB id:

2mjw

Name:

Signaling protein/metal binding protein

Title:

Structural insights into calcium bound s100p - v domain of the receptor for advanced glycation end products (rage) complex

Structure:

Advanced glycosylation end product-specific receptor. Chain: a, c. Fragment: unp residues 23-121. Synonym: receptor for advanced glycosylation end products. Engineered: yes. Protein s100-p. Chain: b, d. Fragment: unp residues 1-94. Synonym: migration-inducing gene 9 protein, mig9, protein s100-e,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ager, rage. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: s100p, s100e.

NMR struc:

10 models

Authors:

P.S.Rao

Key ref:

S.R.Penumutchu et al. (2014). Structural insights into calcium-bound S100P and the V domain of the RAGE complex. Plos One, 9, e103947. PubMed id: 25084534 DOI: 10.1371/journal.pone.0103947

Date:

19-Jan-14 Release date: 05-Nov-14

Protein chains

Q15109  (RAGE_HUMAN) -  Advanced glycosylation end product-specific receptor from Homo sapiens

Seq: 404 a.a.

Struc: 101 a.a.*

Protein chains

P25815  (S100P_HUMAN) -  Protein S100-P from Homo sapiens

Seq: 95 a.a.

Struc: 94 a.a.

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

DOI no: 10.1371/journal.pone.0103947

Plos One 9:e103947 (2014)

PubMed id: 25084534

Structural insights into calcium-bound S100P and the V domain of the RAGE complex.

S.R.Penumutchu, R.H.Chou, C.Yu.

ABSTRACT

The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE) and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+)-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC), fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2)-bound S100P was found to lie in the micromolar range (Kd of ∼ 6 µM). NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.