Báo cáo khoa học: Biological role of bacterial inclusion bodies: a model for amyloid aggregation

MINIREVIEW

Biological role of bacterial inclusion bodies: a model for

amyloid aggregation

Elena Garcı´a-Fruito´ s1–3,*, Raimon Sabate1,4,*, Natalia S. de Groot1,4, Antonio Villaverde1–3 and

Salvador Ventura1,4

1 Institute for Biotechnology and Biomedicine, Universitat Auto`noma de Barcelona, Spain

2 Department of Genetics and Microbiology, Universitat Auto`noma de Barcelona, Spain

3 CIBER de Bioingenierı´a, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain

4 Department of Biochemistry and Molecular Biology, Universitat Auto`noma de Barcelona, Spain

Biotechnology of bacterial inclusion

bodies; a historical view

Production of recombinant proteins in microorgan￾isms, powered in the late 1970s by the identification of

restriction enzymes, has provided much fewer products

than initially expected [1]. The ready-to-use concept of

recombinant DNA technologies has proved to be unre￾alistic and has faced severe obstacles associated with

the physiology of the host microorganism. This is

because the cellular protein factories are usually forced

to produce heterologous polypeptides, encoded in a

multicopy expression plasmid, over physiological rates

Keywords

aggregation; amyloid; FTIR; inclusion bodies;

protein folding; protein quality; recombinant

proteins

Correspondence

A. Villaverde, Institute for Biotechnology and

Biomedicine, Universitat Auto`noma de

Barcelona, Bellaterra, 08193 Barcelona,

Spain

Fax: +34 93 581 2011

Tel: +34 93 581 2148

E-mail: [email protected]

S. Ventura, Institute for Biotechnology and

Biomedicine, Universitat Auto`noma de

Barcelona, Bellaterra, 08193 Barcelona,

Spain

Fax: +34 93 581 2011

Tel: +34 93 586 8956

E-mail: [email protected]

*These authors contributed equally to this

work

(Received 28 January 2011, revised 18

March 2011, accepted 15 April 2011)

doi:10.1111/j.1742-4658.2011.08165.x

Inclusion bodies are insoluble protein aggregates usually found in recombi￾nant bacteria when they are forced to produce heterologous protein species.

These particles are formed by polypeptides that cross-interact through

sterospecific contacts and that are steadily deposited in either the cell’s

cytoplasm or the periplasm. An important fraction of eukaryotic proteins

form inclusion bodies in bacteria, which has posed major problems in the

development of the biotechnology industry. Over the last decade, the fine

dissection of the quality control system in bacteria and the recognition of

the amyloid-like architecture of inclusion bodies have provided dramatic

insights on the dynamic biology of these aggregates. We discuss here the

relevant aspects, in the interface between cell physiology and structural

biology, which make inclusion bodies unique models for the study of pro￾tein aggregation, amyloid formation and prion biology in a physiologically

relevant background.

Abbreviations

IB, inclusion body; PFD, prion forming domain.

FEBS Journal 278 (2011) 2419–2427 ª 2011 The Authors Journal compilation ª 2011 FEBS 2419