6gaj

Crystal structure of the T1L reovirus sigma1 coiled coil tail (iodide)

spinqualitylabelsall models 6gaj, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gaj is a 3 chain structure with sequence from Mammalian orthoreovirus 1 Lang. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.35Å Ligands: CL, IOD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SIGM1_REOVL Fiber-like molecule that attaches the virion to the host cell membrane by binding to the primary receptor F11R/JAM-A and to sialic acid containing proteins (coreceptor). The interaction of sigma-1 with F11R is required for NF-kB activation and apoptosis. Binding to both sialic acid and F11R is required to induce maximal levels of apoptosis (By similarity). Publication Abstract from PubMed Mammalian orthoreovirus attachment to target cells is mediated by outer-capsid protein sigma1, which projects from the virion surface. The sigma1 protein is a homotrimer consisting of a filamentous tail, which is partly inserted into the virion, a body domain constructed from beta-spiral repeats, and a globular head with receptor-binding properties. The sigma1 tail is predicted to form an alpha-helical coiled coil. Although sigma1 undergoes a conformational change during cell entry, the nature of this change and its contributions to viral replication are unknown. Electron micrographs of sigma1 molecules released from virions identified three regions of flexibility, including at the midpoint of the molecule, that may be involved in its structural rearrangement. To enable a detailed understanding of essential sigma1 tail organization and properties, we determined high-resolution structures of the reovirus type 1 Lang (T1L) and type 3 Dearing (T3D) sigma1 tail domains. Both molecules feature extended alpha-helical coiled coils, with T1L sigma1 harboring central chloride ions. Each molecule displays a discontinuity (stutter) within the coiled coil and an unexpectedly seamless transition to the body domain. The transition region features conserved interdomain interactions and appears rigid rather than highly flexible. Functional analyses of reoviruses containing engineered sigma1 mutations suggest that conserved residues predicted to stabilize the coiled coil-to-body junction are essential for sigma1 folding and encapsidation, whereas central chloride ion coordination and the stutter are dispensable for efficient replication. Together, these findings enable modeling of full-length reovirus sigma1 and provide insight into the stabilization of a multi-domain viral attachment protein.IMPORTANCE While it is established that different conformational states of attachment proteins of enveloped viruses mediate receptor binding and membrane fusion, less is understood about how such proteins mediate attachment and entry in nonenveloped viruses. The filamentous reovirus attachment protein, sigma1, binds cellular receptors, contains regions of predicted flexibility including at the fiber midpoint, and undergoes a conformational change during cell entry. Neither the nature of the structural change nor its contribution to viral infection is understood. We determined crystal structures of large sigma1 fragments for two different reovirus serotypes. We observed an unexpectedly tight transition between two domains spanning the fiber midpoint, which allows for little flexibility. Studies of reoviruses with engineered changes near the sigma1 midpoint suggest that the stabilization of this region is critical for function. Together with a previously determined structure, we now have a complete model of the full-length, elongated reovirus sigma1 attachment protein. Structural and Functional Features of the Reovirus sigma1 Tail.,Dietrich MH, Ogden KM, Long JM, Ebenhoch R, Thor A, Dermody TS, Stehle T J Virol. 2018 Apr 25. pii: JVI.00336-18. doi: 10.1128/JVI.00336-18. PMID:29695426 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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