Inter-Molecular Electrostatic Interactions Stabilizing the Structure of the PD-1/PD-L1 Axis: A Structural Evolutionary Perspective

Wei Li

doi:10.20944/preprints202001.0130.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 12 January 2020 / Approved: 12 January 2020 / Online: 12 January 2020 (16:58:35 CET)

PD-1/PD-L1 axis is one key therapeutic target against tumor cell immune escape. Structurally essential to the PD-1/PD-L1-linked immune escape is the binding interface of the PD-1/PD-L1 complex structure. Incorporating currently available PD-1/PD-L1-related experimental structures, this article unveils two sets of experimentally observed inter-molecular electrostatic interactions which stabilize the binding interface of the PD-1/PD-L1 complex structure. For the first time, this article proposes an evolutionary structural hypothesis that, as a result of natural selection, PD-1 is able to genetically mutate itself to structurally disrupt the PD-1/PD-L1 axis towards the restoration of T cell-mediated anti-tumor immunity.

PD-1; PD-L1; Cancer-linked genetic mutation; Electrostatic repulsion; Structural evolution

Biology and Life Sciences, Biology and Biotechnology

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Inter-Molecular Electrostatic Interactions Stabilizing the Structure of the PD-1/PD-L1 Axis: A Structural Evolutionary Perspective

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