Structural proteomics, electron cryo-microscopy and structural modeling approaches in bacteria-human protein interactions

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T1 - Structural proteomics, electron cryo-microscopy and structural modeling approaches in bacteria-human protein interactions

AU - Chowdhury, Sounak

AU - Happonen, Lotta

AU - Khakzad, Hamed

AU - Malmström, Lars

AU - Malmström, Johan

PY - 2020/2/19

Y1 - 2020/2/19

N2 - A central challenge in infection medicine is to determine the structure and function of host-pathogen protein-protein interactions to understand how these interactions facilitate bacterial adhesion, dissemination and survival. In this review, we focus on proteomics, electron cryo-microscopy and structural modeling to showcase instances where affinity-purification (AP) and cross-linking (XL) mass spectrometry (MS) has advanced our understanding of host-pathogen interactions. We highlight cases where XL-MS in combination with structural modeling has provided insight into the quaternary structure of interspecies protein complexes. We further exemplify how electron cryo-tomography has been used to visualize bacterial-human interactions during attachment and infection. Lastly, we discuss how AP-MS, XL-MS and electron cryo-microscopy and -tomography together with structural modeling approaches can be used in future studies to broaden our knowledge regarding the function, dynamics and evolution of such interactions. This knowledge will be of relevance for future drug and vaccine development programs.

AB - A central challenge in infection medicine is to determine the structure and function of host-pathogen protein-protein interactions to understand how these interactions facilitate bacterial adhesion, dissemination and survival. In this review, we focus on proteomics, electron cryo-microscopy and structural modeling to showcase instances where affinity-purification (AP) and cross-linking (XL) mass spectrometry (MS) has advanced our understanding of host-pathogen interactions. We highlight cases where XL-MS in combination with structural modeling has provided insight into the quaternary structure of interspecies protein complexes. We further exemplify how electron cryo-tomography has been used to visualize bacterial-human interactions during attachment and infection. Lastly, we discuss how AP-MS, XL-MS and electron cryo-microscopy and -tomography together with structural modeling approaches can be used in future studies to broaden our knowledge regarding the function, dynamics and evolution of such interactions. This knowledge will be of relevance for future drug and vaccine development programs.

U2 - 10.1007/s00430-020-00663-5

DO - 10.1007/s00430-020-00663-5

M3 - Review article

JO - Medical microbiology and immunology

JF - Medical microbiology and immunology

SN - 0300-8584

ER -