Distinct Activities of Escherichia coli Small Heat Shock Proteins IbpA and IbpB Promote Efficient Protein Disaggregation

作者：Ratajczak Elzbieta; Zietkiewicz Szymon; Liberek Krzysztof^*

来源：Journal of Molecular Biology, 2009, 386(1): 178-189.

DOI：10.1016/j.jmb.2008.12.009

• small heat shock proteins
• protein aggregation
• protein disaggregation
• Hsp70
• Hsp100

It has been proposed that small heat shock proteins (sHsps) associate with aggregated proteins and change their physical properties in such a way that chaperone-mediated disaggregation and refolding become much more efficient. Here, we investigate the influence of two Escherichia coli sHsps, IbpA and lbpB, on the properties of aggregates formed under heat shock conditions and the susceptibility of these aggregates to chaperone-dependent reactivation. Our results show that the presence of IbpA during heat denaturation is sufficient to change the macroscopic properties of aggregates. The aggregates are substantially smaller than aggregates formed in the absence of sHsps and they are stained differently on electron micrographs. Moreover, these aggregates are indistinguishable, by electron microscopy studies and sedimentation analysis, from aggregates obtained during heat denaturation in the presence of IbpA and IbpB. However, the morphological similarity between these two types of aggregates does not correlate with similar susceptibility to Hsp100-Hsp70-dependent reactivation. The presence of IbpA alone during substrate denaturation does not increase the efficiency of the subsequent Hsp100-Hsp70-dependent reactivation. On the contrary, substantial inhibition of this process is observed. IbpB associates with aggregates at high temperature due to its interaction with fbpA and releases the IbpA-mediated inhibitory effect. Our results suggest there is an interplay between IbpA and IbpB in promoting Hsp100-Hsp70-mediated disaggregation of protein aggregates. Although each seems to play a different role in this process, they cooperate to stabilize protein aggregates in a disaggregation-competent state.

• 出版日期2009-2-13