Dimerisation and structural integrity of Heparin Binding Hemagglutinin A from Mycobacterium tuberculosis: Implications for bacterial agglutination

Esposito, Carla; Carullo, Paola; Pedone, Emilia; Graziano, Giuseppe; Vecchio, Pompea Del; Berisio, Rita

doi:10.1016/j.febslet.2010.02.044

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Volume 584, Issue 6 , Pages 1091-1096, 19 March 2010

Dimerisation and structural integrity of Heparin Binding Hemagglutinin A from Mycobacterium tuberculosis: Implications for bacterial agglutination

Edited by Renee Tsolis

Carla Esposito
- Istitute of Biostructures and Bioimaging, C.N.R., I-80134 – Naples, Italy
Paola Carullo
- Department of Chemistry “Paolo Corradini”, University of Naples Federico II, Complesso Universitario Monte S. Angelo, I-80126, Naples, Italy
Emilia Pedone
- Istitute of Biostructures and Bioimaging, C.N.R., I-80134 – Naples, Italy
Giuseppe Graziano
- Department of Biological and Environmental Sciences, University of Sannio, I-82100 Benevento, Italy
Pompea Del Vecchio
- Department of Chemistry “Paolo Corradini”, University of Naples Federico II, Complesso Universitario Monte S. Angelo, I-80126, Naples, Italy
Rita Berisio
- Istitute of Biostructures and Bioimaging, C.N.R., I-80134 – Naples, Italy
- Corresponding author. Fax: +390812536642.

Received 20 January 2010; received in revised form 12 February 2010; accepted 16 February 2010. published online 22 February 2010.

Abstract

Heparin Binding Hemagglutinin A (HBHA) is hitherto the sole virulence factor associated with tuberculosis dissemination from the lungs, the site of primary infection, to epithelial cells. We have previously reported the solution structure of HBHA, a dimeric and elongated molecule. Since oligomerisation of HBHA is associated with its ability to induce bacterial agglutination, we investigated this process using experimental and modelling techniques. We here identified a short segment of HBHA whose presence is mandatory for the stability of folded conformation, whose denaturation is a reversible two-state process. Our data suggest that agglutination-driven cell–cell interactions do not occur via association of HBHA monomers, nor via association of HBHA dimers and open the scenario to a possible trans-dimerisation process.

Structured summary

MINT-7709940, MINT-7709948: HBHA (uniprotkb:A5TZK3) and HBHA (uniprotkb:A5TZK3) bind (MI:0407) by circular dichroism (MI:0016)MINT-7709966: HBHA (uniprotkb:A5TZK3) and HBHA (uniprotkb:A5TZK3) bind (MI:0407) by biophysical (MI:0013)MINT-7709955: HBHA (uniprotkb:A5TZK3) and HBHA (uniprotkb:A5TZK3) bind (MI:0407) by dynamic light scattering (MI:0038)