Small Heat Shock Protein16.3 of Mycobacterium tuberculosis: After Two Decades of Functional Characterization

Abstract

Small heat shock proteins (sHSPs) are one of the five families of proteins acting as molecular chaperone. sHSPs possess a universally conserved alpha-crystallin domain, hence, also known as alpha-crystallin family. Mycobacterium tuberculosis (MTB) is an etiological agent of tuberculosis, a disease claiming million of lives every year across the world. MTB has two sHSPs: sHSP16.3 (a 16.3 kDa protein) and Acr2 (a 17.8 kDa protein). Of these, sHSP16.3 has been reported to be crucial for survival of MTB during prolonged period of dormancy, in addition to indispensable role in its growth, virulence and cell wall thickening. Additionally, this mycobacterial protein is also beneficial for host as well. Due to strong immunogenic properties and consistent presence in patients sera, sHSP16.3 has largely been implicated in vaccine development and diagnosis of latent and active infections of MTB in the clinical cases of TB. Recently, our study provided the substantial evidence to exploit this mycobacterial protein as a good drug target for developing novel therapeutic intervention. In the present review, a comprehensive analysis of various attributes of sHSP16.3 has been done and major gaps in area have been highlighted for future course of action.

Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis

“…An interesting example of a bacterial crystallin homolog is Hsp16.3 in Mycobacterium tuberculosis. Functioning as a chaperone, this protein is able to facilitate the survival of the bacterium by promoting the dormant state during stress (Jee et al, 2018). Similarly, the chaperone sHsp16 in Trypanosoma cruzi functions by allowing the organism to resist oxidative and heat stress (Perez-Morales et al, 2009).…”

Role of Molecular Interactions and Oligomerization in Chaperone Activity of Recombinant Acr from Mycobacterium tuberculosis

“…This is probably the basic mechanism by which heat shock proteins can prevent unfolding of proteins. The status of oligomerization of recombinant Acr protein affects chaperone activity against insulin B chain aggregation.Recent in silico studies on Acr have again assumed it to be a dodecamer (15).The potential of Acr as a diagnostic and vaccine is largely unfulfilled even 20 years after its discovery (16,17).…”

“…A clear trend of increase in inhibition was observed with increase in molar concentration of Acr ( Table 2). The amount of Acr molecules used to inhibit insulin was calculated in terms of number of molecules and it was found that this number ranged from 0.6 x 10 16 to 1.5 x 10 16 while the insulin B chain molecules ranged from 1.8 x 10 15 to 1.05 x 10 16 , wherein, more than 50% of the insulin B chain was covered, and the complete inhibition of aggregation was achieved ( Fig. 2a).…”

“…The assumption is that Acr is 18 kDa and the insulin B chain is 3 kDa. The number of molecules of insulin has been calculated based on an assay volume of 0.25 ml and the number of insulin molecules assumed to be 1.08 x1016 .…”

ПРИМЕНЕНИЕ ТЕХНОЛОГИИ Fc-СЛИЯНИЯ БЕЛКОВ ДЛЯ РАЗРАБОТКИ ВАКЦИН ПРОТИВ ИНФЕКЦИОННЫХ БОЛЕЗНЕЙ ЖИВОТНЫХ И ЧЕЛОВЕКА

“…Он высокоиммуногенный и может вызывать сильный клеточный иммунный ответ у пациентов, подвергшихся воздействию Mtb. Секретируемые белки -антигены Mtb10.4 (Rv0288), Mtb8.4 (Rv1174c), ESAT-6 (Rv3875) и Ag85B (Rv1886c) тоже высокоиммуногенные и способны обеспечить сильный защитный иммунитет против заражения M. tuberculosis, что позволяет предположить, что это перспективные кандидатные антигены (53,54).…”