Principles of assembly reveal a periodic table of protein complexes

Abstract

Structural insights into protein complexes have had a broad impact on our understanding of biological function and evolution. In this work, we sought a comprehensive understanding of the general principles underlying quaternary structure organization in protein complexes. We first examined the fundamental steps by which protein complexes can assemble, using experimental and structure-based characterization of assembly pathways. Most assembly transitions can be classified into three basic types, which can then be used to exhaustively enumerate a large set of possible quaternary structure topologies. These topologies, which include the vast majority of observed protein complex structures, enable a natural organization of protein complexes into a periodic table. On the basis of this table, we can accurately predict the expected frequencies of quaternary structure topologies, including those not yet observed. These results have important implications for quaternary structure prediction, modeling, and engineering.

Nanoparticle Assembly:A Perspective and some Unanswered Questions

“…In line with the work on the periodic table of protein complexes 30 and the biomimetic nature of NPs, is it possible to enumerate all possible aggregate motifs? It will be valuable to list the minimum number of parameters required to capture all possible motifs, e.g.…”

Nondeterministic self-assembly with asymmetric interactions

“…While most chemical and physical selfassembly processes tend to be non-deterministic, most self-assembly processes in biology are deterministic, as the development and functioning of biological organisms requires that biological structures, from the molecular to the macroscopic, are formed repeatedly and accurately. The most prominent example is the enormous variety of protein complexes [1][2][3], which fulfil important biological functions in all species, from bacteria to humans. For protein complexes to function in their respective context, their physical structures have to be correct, which means that the assembly process has to be deterministic in the sense that it must always lead to the same final structure.…”

“…Self-assembling systems are ubiquitous in nature, with many examples in biology, chemistry, and physics, including protein complexes [1][2][3], DNA tiles [4,5], colloids [6], micelles [7], and diffusion-limited aggregation (DLA) [8]. While most chemical and physical selfassembly processes tend to be non-deterministic, most self-assembly processes in biology are deterministic, as the development and functioning of biological organisms requires that biological structures, from the molecular to the macroscopic, are formed repeatedly and accurately.…”

Cooperative Subunit Refolding of a Light‐Harvesting Protein through a Self‐Chaperone Mechanism

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Abstract: The fold of ap rotein is encoded by its amino acid sequence,b ut how complex multimeric proteins fold and assemble into functional quaternary structures remains unclear.H ere we show that two structurally different phycobiliproteins refold and reassemble in ac ooperative manner from their unfolded polypeptide subunits,w ithout biological chaperones.R efolding was confirmed by ultrafast broadband transient absorption and two-dimensional electronic spectroscopyt op robe internal chromophores as am arker of quaternary structure.O ur results demonstrate ac ooperative,s elfchaperone refolding mechanism, whereby the b-subunits independently refold, therebyt emplating the folding of the asubunits,w hich then chaperone the assembly of the native complex, quantitatively returning all coherences.O ur results indicate that subunit self-chaperoning is ar obust mechanism for heteromeric protein folding and assembly that could also be applied in self-assembled synthetic hierarchical systems.The folding of proteins was shown to be encoded by amino acids in 1960s.[1] Cooperativity [2][3][4] and the realization that multiple folding pathways are possible [5] are the keys to resolving Levinthalsf amous paradox, [6] which states that if aprotein were to explore all possible conformations,itwould take longer than the age of the universe to fold-yet most proteins fold within seconds.M any proteins in nature are found as multimeric or quaternary complexes, [7] with database searches suggesting that more than 80 %o fp roteins are multimeric,w ith between 15-50 %b eing hetero-oligomeric. [8,9] Thep revailing view on how these complexes form starts with the assumption that the individual subunits are first folded, or sometimes disordered (fuzzy), prior to the oligomerization step.

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“…[1] Cooperativity [2][3][4] and the realization that multiple folding pathways are possible [5] are the keys to resolving Levinthalsf amous paradox, [6] which states that if aprotein were to explore all possible conformations,itwould take longer than the age of the universe to fold-yet most proteins fold within seconds.M any proteins in nature are found as multimeric or quaternary complexes, [7] with database searches suggesting that more than 80 %o fp roteins are multimeric,w ith between 15-50 %b eing hetero-oligomeric. [8,9] Thep revailing view on how these complexes form starts with the assumption that the individual subunits are first folded, or sometimes disordered (fuzzy), prior to the oligomerization step.…”