Assembly principles and structure of a 6.5-MDa bacterial microcompartment shell

Abstract

Many bacteria contain primitive organelles composed entirely of protein. These bacterial microcompartments share a common architecture of an enzymatic core encapsulated in a selectively permeable protein shell; prominent examples include the carboxysome for CO2 fixation and catabolic microcompartments found in many pathogenic microbes. The shell sequesters enzymatic reactions from the cytosol, analogous to the lipid-based membrane of eukaryotic organelles. Despite available structural information for single building blocks, the principles of shell assembly have remained elusive. We present the crystal structure of an intact shell from Haliangium ochraceum, revealing the basic principles of bacterial microcompartment shell construction. Given the conservation among shell proteins of all bacterial microcompartments, these principles apply to functionally diverse organelles and can inform the design and engineering of shells with new functionalities.

Prokaryotic nanocompartments form synthetic organelles in a eukaryote

“…Other proteinaceous organelles, such as bacterial microcompartments, are comprised of many different protein subunits and thus entail a higher degree of complexity. Although significant progress has been made towards understanding the molecular principles governing these complex systems 1,10 , our incomplete understanding is still a bottleneck for repurposing such systems as synthetic organelles.…”

“…The ability to incorporate similar functional properties in engineered organisms could lead to significant improvements in metabolic engineering and recombinant protein expression 5,6 . However, efforts to reprogram naturally-occurring compartments for synthetic applications are challenging due to their inherent complexity and the large number of different biomacromolecules involved [7][8][9][10] . We therefore identified the encapsulin family of self-assembling prokaryotic proteins as a highly engineerable candidate suitable for designing programmable synthetic organelles in eukaryotes within their interior as part of the self-assembly process to tailor the activity of packaged components.…”

Bacterial microcompartments

“…Recognition of the homology among BMC shell proteins using bioinformatics has led to the identification of a multitude of functionally diverse BMCs, found across 19 out of the 29 established bacterial phyla and also in several candidate phyla (Figure 2A) 6 . Moreover, new methods of visualization such as atomic force microscopy 19 , the crystal structure determination of an intact BMC shell 20 and labeling BMCs with fluorescent proteins 21–23 have provided new insights into BMC structure, assembly and subcellular localization. This knowledge has enabled the engineering of BMCs for new applications in synthetic biology 24–26 .…”

Harnessing the power of microbial nanowires

“…The geometric assembly of proteins leads, for example, to the formation of molecular nanomachines and hyperstructures such as the ATP synthase complex and the cytoskeletal microtubules respectively (Alfaro‐Aco and Petry, 2015; Ruhle and Leister, 2015). Proteins can also self‐assemble in planar geometric configurations to make the S‐layer lattices of some bacteria and archaea (Sleytr et al ., 2014) and into distinctive 3D geometries such as bacterial intracellular microcompartments and viral capsids (Uetrecht et al ., 2011; Sutter et al ., 2017). These natural designs have inspired the synthesis of novel nanomaterials and protocols for protein functionalization and controlled association that modulate the material's properties and enable new functions (Yang et al ., 2016).…”