High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface

Shruti Chatterjee; Shankar V. Kundapura; Aditya J. Basak; Debangshu Mukherjee; Sagarika Dash; Namrata Ganguli; Amit K. Das; Gayatri Mukherjee; Dibyendu Samanta; Udupi A. Ramagopal

doi:10.1016/j.ijbiomac.2022.04.196

High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface

Shruti Chatterjee, Shankar V. Kundapura, Aditya J. Basak, Debangshu Mukherjee, Sagarika Dash, Namrata Ganguli, Amit K. Das, Gayatri Mukherjee, Dibyendu Samanta, Udupi A. Ramagopal

Multiscale Biomedical Systems

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, is predominantly a disease of the lungs acquired by inhaling mycobacteria from infected individuals via airborne droplets. In order to facilitate their entry into the alveolar macrophages, mycobacteria have a collection of pathogen-associated molecular patterns (PAMPs) on their surface that are known to detect certain pattern recognition receptors present on the surface of host cells. A major group of these PAMPs includes mycobacterial lipoproteins, of which, the 19 kDa surface antigen LpqH, has been reported to play a critical role in both host-pathogen interactions as well as pleiotropic immune regulation. Despite its crucial involvement in tuberculosis, the detailed structure-function relationship of this protein remains to be explored. Here, we report the high-resolution crystal structure of the non-acylated LpqH (LpqH^48–159) at a resolution of 1.26 Å, which adopts a unique fold. Flow cytometry-based experiments show that the protein can bind and induce apoptosis in PMA-activated human monocytic cell line THP-1, indicative of the preservation of functionality of the protein. Furthermore, analysis of conservation of LpqH sequences from Mycobacterium species reveals a patch of conserved residues on the surface which may play a role in its binding partner recognition and hence in host-pathogen interaction.

Original language	English
Pages (from-to)	494-503
Number of pages	10
Journal	International Journal of Biological Macromolecules
Volume	210
DOIs	https://doi.org/10.1016/j.ijbiomac.2022.04.196
State	Published - Jun 15 2022

Funding

The authors wish to acknowledge Snigdha Maiti and Dr. Kheerthana Duraivelan for helpful discussions throughout the course of this work. This work was funded by STARS-MHRD (STARS/298/2019), Government of India to DS; and SERB (ECR/2017/002073), Government of India to GM. SC, AJB, DM, SD and NG are supported by fellowship provided by Indian Institute of Technology Kharagpur, Government of India. UAR would like to acknowledge funding from the DST/SERB (EMR/2016/003970), Government of India and Admar Mutt Education Foundation (AMEF) for the support. SVK acknowledges KSTePS, DST, Government of Karnataka, India for fellowship. We thank the beamline staff at the Elettra XRD2 particularly Dr. Annie Heroux and Dr. Raghurama P. Hegde for beamline support. Access to the XRD2 beamline at the Elettra Sincrotrone, Trieste was made possible through grant-in-aid from the Department of Science and Technology (DST), India, vide grant number DSTO-1668. The authors wish to acknowledge Snigdha Maiti and Dr. Kheerthana Duraivelan for helpful discussions throughout the course of this work. This work was funded by STARS-MHRD ( STARS/298/2019 ), Government of India to DS; and SERB ( ECR/2017/002073 ), Government of India to GM. SC, AJB, DM, SD and NG are supported by fellowship provided by Indian Institute of Technology Kharagpur, Government of India. UAR would like to acknowledge funding from the DST/SERB ( EMR/2016/003970 ), Government of India and Admar Mutt Education Foundation ( AMEF ) for the support. SVK acknowledges KSTePS, DST, Government of Karnataka, India for fellowship. We thank the beamline staff at the Elettra XRD2 particularly Dr. Annie Heroux, and Dr. Raghurama P. Hegde for beamline support. Access to the XRD2 beamline at the Elettra Sincrotrone, Trieste was made possible through grant-in-aid from the Department of Science and Technology (DST), India, vide grant number DSTO-1668.

Keywords

Mycobacterial lipoprotein LpqH
Protein structure
X-ray crystallography

Access to Document

10.1016/j.ijbiomac.2022.04.196

Cite this

Chatterjee, S., Kundapura, S. V., Basak, A. J., Mukherjee, D., Dash, S., Ganguli, N., Das, A. K., Mukherjee, G., Samanta, D., & Ramagopal, U. A. (2022). High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface. International Journal of Biological Macromolecules, 210, 494-503. https://doi.org/10.1016/j.ijbiomac.2022.04.196

@article{365cf687da22450bac9af5440e14fde4,

title = "High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface",

abstract = "Tuberculosis, caused by Mycobacterium tuberculosis, is predominantly a disease of the lungs acquired by inhaling mycobacteria from infected individuals via airborne droplets. In order to facilitate their entry into the alveolar macrophages, mycobacteria have a collection of pathogen-associated molecular patterns (PAMPs) on their surface that are known to detect certain pattern recognition receptors present on the surface of host cells. A major group of these PAMPs includes mycobacterial lipoproteins, of which, the 19 kDa surface antigen LpqH, has been reported to play a critical role in both host-pathogen interactions as well as pleiotropic immune regulation. Despite its crucial involvement in tuberculosis, the detailed structure-function relationship of this protein remains to be explored. Here, we report the high-resolution crystal structure of the non-acylated LpqH (LpqH48–159) at a resolution of 1.26 {\AA}, which adopts a unique fold. Flow cytometry-based experiments show that the protein can bind and induce apoptosis in PMA-activated human monocytic cell line THP-1, indicative of the preservation of functionality of the protein. Furthermore, analysis of conservation of LpqH sequences from Mycobacterium species reveals a patch of conserved residues on the surface which may play a role in its binding partner recognition and hence in host-pathogen interaction.",

keywords = "Mycobacterial lipoprotein LpqH, Protein structure, X-ray crystallography",

author = "Shruti Chatterjee and Kundapura, {Shankar V.} and Basak, {Aditya J.} and Debangshu Mukherjee and Sagarika Dash and Namrata Ganguli and Das, {Amit K.} and Gayatri Mukherjee and Dibyendu Samanta and Ramagopal, {Udupi A.}",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = jun,

day = "15",

doi = "10.1016/j.ijbiomac.2022.04.196",

language = "English",

volume = "210",

pages = "494--503",

journal = "International Journal of Biological Macromolecules",

issn = "0141-8130",

publisher = "Elsevier",

}

Chatterjee, S, Kundapura, SV, Basak, AJ, Mukherjee, D, Dash, S, Ganguli, N, Das, AK, Mukherjee, G, Samanta, D & Ramagopal, UA 2022, 'High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface', International Journal of Biological Macromolecules, vol. 210, pp. 494-503. https://doi.org/10.1016/j.ijbiomac.2022.04.196

High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface. / Chatterjee, Shruti; Kundapura, Shankar V.; Basak, Aditya J. et al.
In: International Journal of Biological Macromolecules, Vol. 210, 15.06.2022, p. 494-503.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface

AU - Chatterjee, Shruti

AU - Kundapura, Shankar V.

AU - Basak, Aditya J.

AU - Mukherjee, Debangshu

AU - Dash, Sagarika

AU - Ganguli, Namrata

AU - Das, Amit K.

AU - Mukherjee, Gayatri

AU - Samanta, Dibyendu

AU - Ramagopal, Udupi A.

PY - 2022/6/15

Y1 - 2022/6/15

N2 - Tuberculosis, caused by Mycobacterium tuberculosis, is predominantly a disease of the lungs acquired by inhaling mycobacteria from infected individuals via airborne droplets. In order to facilitate their entry into the alveolar macrophages, mycobacteria have a collection of pathogen-associated molecular patterns (PAMPs) on their surface that are known to detect certain pattern recognition receptors present on the surface of host cells. A major group of these PAMPs includes mycobacterial lipoproteins, of which, the 19 kDa surface antigen LpqH, has been reported to play a critical role in both host-pathogen interactions as well as pleiotropic immune regulation. Despite its crucial involvement in tuberculosis, the detailed structure-function relationship of this protein remains to be explored. Here, we report the high-resolution crystal structure of the non-acylated LpqH (LpqH48–159) at a resolution of 1.26 Å, which adopts a unique fold. Flow cytometry-based experiments show that the protein can bind and induce apoptosis in PMA-activated human monocytic cell line THP-1, indicative of the preservation of functionality of the protein. Furthermore, analysis of conservation of LpqH sequences from Mycobacterium species reveals a patch of conserved residues on the surface which may play a role in its binding partner recognition and hence in host-pathogen interaction.

AB - Tuberculosis, caused by Mycobacterium tuberculosis, is predominantly a disease of the lungs acquired by inhaling mycobacteria from infected individuals via airborne droplets. In order to facilitate their entry into the alveolar macrophages, mycobacteria have a collection of pathogen-associated molecular patterns (PAMPs) on their surface that are known to detect certain pattern recognition receptors present on the surface of host cells. A major group of these PAMPs includes mycobacterial lipoproteins, of which, the 19 kDa surface antigen LpqH, has been reported to play a critical role in both host-pathogen interactions as well as pleiotropic immune regulation. Despite its crucial involvement in tuberculosis, the detailed structure-function relationship of this protein remains to be explored. Here, we report the high-resolution crystal structure of the non-acylated LpqH (LpqH48–159) at a resolution of 1.26 Å, which adopts a unique fold. Flow cytometry-based experiments show that the protein can bind and induce apoptosis in PMA-activated human monocytic cell line THP-1, indicative of the preservation of functionality of the protein. Furthermore, analysis of conservation of LpqH sequences from Mycobacterium species reveals a patch of conserved residues on the surface which may play a role in its binding partner recognition and hence in host-pathogen interaction.

KW - Mycobacterial lipoprotein LpqH

KW - Protein structure

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=85129509030&partnerID=8YFLogxK

U2 - 10.1016/j.ijbiomac.2022.04.196

DO - 10.1016/j.ijbiomac.2022.04.196

M3 - Article

C2 - 35504420

AN - SCOPUS:85129509030

SN - 0141-8130

VL - 210

SP - 494

EP - 503

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

ER -

High-resolution crystal structure of LpqH, an immunomodulatory surface lipoprotein of Mycobacterium tuberculosis reveals a distinct fold and a conserved cleft on its surface

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this