TdfH selectively binds metal-loaded tetrameric calprotectin for zinc import

Aloke K Bera,Simone Harrison,Runrun Wu,Nicholas Noinaj,Cynthia Nau Cornelissen,Walter J Chazin

doi:10.1038/s42003-022-03039-y

Aloke K Bera, Simone Harrison + Show 4 more

Open Access

https://doi.org/10.1038/s42003-022-03039-y

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Abstract

To combat nutritional immunity, N. gonorrhoeae has evolved systems to hijack zinc and other metals directly from host metal-binding proteins such as calprotectin (CP). Here, we report the 6.1 Å cryoEM structure of the gonococcal surface receptor TdfH in complex with a zinc-bound CP tetramer. We further show that TdfH can also interact with CP in the presence of copper and manganese, but not with cobalt.

Highlights

To combat nutritional immunity, N. gonorrhoeae has evolved systems to hijack zinc and other metals directly from host metal-binding proteins such as calprotectin (CP)
Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which can lead to more serious conditions including bacteremia, increased risk of HIV/ AIDS, and infertility[1,2]
No binding was observed with just calcium or zinc alone, or in the presence of ethylenediaminetetraacetic acid (EDTA) (Fig. 1b; lanes 9–11)

Summary

Introduction

N. gonorrhoeae has evolved systems to hijack zinc and other metals directly from host metal-binding proteins such as calprotectin (CP). TdfH was bound to Streptavidin MagneSphere Paramagnetic Particles and assayed for binding under various CP buffer conditions. Experiments reported here demonstrate that both calcium and zinc are required for the stable interaction between CP and TdfH and that the order of calcium or zinc addition to CP has no effect on the complex formation (Fig. 1b; lanes 12–14).

Results

Conclusion