8IQR

Crystal structure of Anti-PEG antibody M9 Fv-clasp fragment with PEG (co-crystallization with PEG550DME)

Summary for 8IQR

• Entry DOI: 10.2210/pdb8iqr/pdb
• Descriptor: M9 VL-SARAH, M9 VH-SARAH, 2,5,8,11,14,17,20,23,26-nonaoxaoctacosane, ... (4 entities in total)
• Functional Keywords: immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 4
• Total formula weight: 83226.16

Authors

Mori, T.,Teramoto, T.,Liu, Y.,Mori, T.,Kakuta, Y. (deposition date: 2023-03-17, release date: 2024-03-20, Last modification date: 2025-03-26)

Primary citation

Liu, Y.,Mori, T.,Ito, Y.,Kuroki, K.,Hayashi, S.,Kohda, D.,Shimizu, T.,Ishida, T.,Roffler, S.R.,Kaneko, M.K.,Kato, Y.,Arimori, T.,Teramoto, T.,Takemura, K.,Ishibashi, K.,Katayama, Y.,Maenaka, K.,Kakuta, Y.,Kitao, A.,Mori, T.
The strategy used by naive anti-PEG antibodies to capture flexible and featureless PEG chains.
J Control Release, 380:396-403, 2025

PubMed Abstract: Polyethylene glycol (PEG) is widely used as a standard stealth polymer, although the induction of anti-PEG antibodies and consequent effects have drawn attention in recent years. To date, several anti-PEG antibodies induced by PEG-modified proteins via the T cell-dependent (TD) pathway, in which affinity maturation occurs, have been reported. In contrast, structures of the naïve anti-PEG antibodies before affinity maturation have not been described in the literature. Here, to understand the details of the naïve anti-PEG antibodies capturing PEG, we studied a naïve anti-PEG antibody induced by a PEG-modified liposome in the absence of affinity maturation via the T cell-independent (TI) pathway. The mutation levels, structures as well as in vitro and in silico binding properties of TI and TD anti-PEG antibodies were compared. The TI anti-PEG antibody showed no mutation and a low binding affinity toward PEG, meanwhile, it allowed PEG chain sliding and weak interaction with the terminal group. Furthermore, the naïve anti-PEG antibodies may obtain high affinities by forming tunnel structures via minimal mutations. This research provides new insights into polymer-antibody interactions, which can facilitate the development of novel stealth polymers that can avoid antibody induction.

PubMed: 39921032
DOI: 10.1016/j.jconrel.2025.02.001

Experimental method

X-RAY DIFFRACTION (2.35 Å)