8v4q
Myxococcus xanthus EncA 3xHis pore mutant with tetrahedral symmetry
Structural highlights
FunctionENCAP_MYXXD Shell component of a type 1, iron-storage encapsulin nanocompartment. Encapsulin nanocompartments are 32 nm in diameter with an iron- and phosphorus-rich core (4Fe:1P) about 24 nm in diameter. Upon expression in E.coli most particles are 32 nm, 20% are 18 nm. The core is filled with an average of 14 dense granules, 5-6 nm in diameter that are not evenly distributed. Each nanocompartment is estimated to hold 30,000-35,000 Fe atoms (PubMed:25024436, PubMed:31194509). The minor proteins EncB, EncC and EncD probably lie against the interior face of the nanocompartment (Probable).[1] [2] [3] Publication Abstract from PubMedProtein capsids are a widespread form of compartmentalization in nature. Icosahedral symmetry is ubiquitous in capsids derived from spherical viruses, as this geometry maximizes the internal volume that can be enclosed within. Despite the strong preference for icosahedral symmetry, we show that simple point mutations in a virus-like capsid can drive the assembly of unique symmetry-reduced structures. Starting with the encapsulin from Myxococcus xanthus, a 180-mer bacterial capsid that adopts the well-studied viral HK97 fold, we use mass photometry and native charge detection mass spectrometry to identify a triple histidine point mutant that forms smaller dimorphic assemblies. Using cryoelectron microscopy, we determine the structures of a precedented 60-mer icosahedral assembly and an unexpected 36-mer tetrahedron that features significant geometric rearrangements around a new interaction surface between capsid protomers. We subsequently find that the tetrahedral assembly can be generated by triple-point mutation to various amino acids and that even a single histidine point mutation is sufficient to form tetrahedra. These findings represent a unique example of tetrahedral geometry when surveying all characterized encapsulins, HK97-like capsids, or indeed any virus-derived capsids reported in the Protein Data Bank, revealing the surprising plasticity of capsid self-assembly that can be accessed through minimal changes in the protein sequence. Point mutation in a virus-like capsid drives symmetry reduction to form tetrahedral cages.,Szyszka TN, Andreas MP, Lie F, Miller LM, Adamson LSR, Fatehi F, Twarock R, Draper BE, Jarrold MF, Giessen TW, Lau YH Proc Natl Acad Sci U S A. 2024 May 14;121(20):e2321260121. doi: , 10.1073/pnas.2321260121. Epub 2024 May 9. PMID:38722807[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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