PDBsum entry 6lyc

Cell adhesion

PDB id: 6lyc

Contents

Protein chains

110 a.a.

17 a.a.

Ligands

ACY

Waters ×70

PDB id:

6lyc

Name:

Cell adhesion

Title:

Crystal structure of the nod sirpa complex with d4-2

Structure:

Sirpa of the nod mouse strain. Chain: a. Engineered: yes. D4-2. Chain: b. Engineered: yes

Source:

Mus musculus. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

1.36Å R-factor: 0.204 R-free: 0.216

Authors:

Y.Murata,M.Matsuda,A.Nakagawa,T.Matozaki

Key ref:

D.Hazama et al. (2020). Macrocyclic Peptide-Mediated Blockade of the CD47-SIRPα Interaction as a Potential Cancer Immunotherapy. Cell Chem Biol, 27, 1181. PubMed id: 32640189 DOI: 10.1016/j.chembiol.2020.06.008

Date:

14-Feb-20 Release date: 01-Jul-20

Protein chain

No UniProt id for this chain

Struc: 110 a.a.

Protein chain

No UniProt id for this chain

Struc: 16 a.a.

DOI no: 10.1016/j.chembiol.2020.06.008

Cell Chem Biol 27:1181 (2020)

PubMed id: 32640189

Macrocyclic Peptide-Mediated Blockade of the CD47-SIRPα Interaction as a Potential Cancer Immunotherapy.

D.Hazama, Y.Yin, Y.Murata, M.Matsuda, T.Okamoto, D.Tanaka, N.Terasaka, J.Zhao, M.Sakamoto, Y.Kakuchi, Y.Saito, T.Kotani, Y.Nishimura, A.Nakagawa, H.Suga, T.Matozaki.

ABSTRACT

Medium-sized macrocyclic peptides are an alternative to small compounds and large biomolecules as a class of pharmaceutics. The CD47-SIRPα signaling axis functions as an innate immune checkpoint that inhibits phagocytosis in phagocytes and has been implicated as a promising target for cancer immunotherapy. The potential of macrocyclic peptides that target this signaling axis as immunotherapeutic agents has remained unknown, however. Here we have developed a macrocyclic peptide consisting of 15 amino acids that binds to the ectodomain of mouse SIRPα and efficiently blocks its interaction with CD47 in an allosteric manner. The peptide markedly promoted the phagocytosis of antibody-opsonized tumor cells by macrophages in vitro as well as enhanced the inhibitory effect of anti-CD20 or anti-gp75 antibodies on tumor formation or metastasis in vivo. Our results suggest that allosteric inhibition of the CD47-SIRPα interaction by macrocyclic peptides is a potential approach to cancer immunotherapy.