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Bacteriophage lambda major capsid protein mutant - W308A
Structural highlights
FunctionCAPSD_LAMBD Assembles to form an icosahedral capsid with a T=7 symmetry. The icosahedral capsid is about 60 nm in diameter and composed of 415 major capsid proteins. The assembly is primed by the interaction between capsid assembly protease and portal dodecamer, and major capsid proteins assemble cooperatively to form the procapsid with the help of capsid scaffolding protein. Major capsid protein forms hexons and pentons of the icosahedron. Viral genomic DNA is packaged into the procapsid through the portal vertex (By similarity). The packaging triggers a dramatic reconfiguration of the capsid shell, expanding from roughly 50nm to 60nm while the capsid thickness decreases. The capsid decoration protein binds the expanded capsid and stabilizes it.[HAMAP-Rule:MF_04133][1] [2] [3] Publication Abstract from PubMedCapsid assembly pathways are strongly conserved in the complex dsDNA viruses, where major capsid proteins (MCP) self-assemble into icosahedral procapsid shells, chaperoned by a scaffolding protein. Without a scaffold, the capsid proteins aggregate and form aberrant structures. This, coupled with the rapid co-polymerization of MCP and scaffolding proteins, has thwarted characterization of the earliest steps in shell assembly. Here we interrogate the structure and biophysical properties of a soluble, assembly-deficient phage lambda major capsid protein, MCP(W308A). The mutant protein is folded, soluble to high concentrations and binds to the scaffolding protein in an apparent SP(2):MCP(W308A)(1) stoichiometry but does not assemble beyond this initiating complex. The MCP(W308A) crystal structure was solved to 2.7 A revealing the canonical HK97 fold in a "pre-assembly" conformation featuring the conserved N-arm and E-loops folded into the body of the protein. Structural, biophysical and computational analyses suggest that MCP(W308A) is thermodynamically trapped in this pre-assembly conformation precluding self-association interactions required for shell assembly. A model is described wherein dynamic interactions between MCP proteins play an essential role in high fidelity viral shell assembly. Scaffold-chaperoned MCP polymerization is a strongly conserved process in all the large dsDNA viruses and our results provide insight into this primordial complex in solution and have broad biological significance in our understanding of virus assembly mechanisms. Characterization of a Primordial Major Capsid-Scaffolding Protein Complex in Icosahedral Virus Shell Assembly.,Davis CR, Backos D, Morais MC, Churchill MEA, Catalano CE J Mol Biol. 2022 Oct 15;434(19):167719. doi: 10.1016/j.jmb.2022.167719. Epub 2022 , Jul 9. PMID:35820453[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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