5X8L

PD-L1 in complex with atezolizumab

Summary for 5X8L

• Entry DOI: 10.2210/pdb5x8l/pdb
• Related: 5X8M
• Descriptor: Programmed cell death 1 ligand 1, atezolizumab light chain, atezolizumab heavy chain (3 entities in total)
• Functional Keywords: complex, antibody, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Isoform 1: Cell membrane ; Single-pass type I membrane protein . Isoform 2: Endomembrane system ; Single-pass type I membrane protein : Q9NZQ7
• Total number of polymer chains: 15
• Total formula weight: 311223.18

Authors

Heo, Y.S.,Lee, H.T. (deposition date: 2017-03-03, release date: 2017-08-16)

Primary citation

Lee, H.T.,Lee, J.Y.,Lim, H.,Lee, S.H.,Moon, Y.J.,Pyo, H.J.,Ryu, S.E.,Shin, W.,Heo, Y.S.
Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
Sci Rep, 7:5532-5532, 2017

PubMed Abstract: In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.

PubMed: 28717238
DOI: 10.1038/s41598-017-06002-8

Experimental method

X-RAY DIFFRACTION (3.1 Å)