8c9m
From Proteopedia
HERV-K Gag immature lattice
Structural highlights
FunctionQ96897_9RETR Capsid protein.[ARBA:ARBA00003374] Matrix protein.[ARBA:ARBA00003230] The products of the Gag polyproteins of infectious retroviruses perform highly complex orchestrated tasks during the assembly, budding, maturation, and infection stages of the viral replication cycle. During viral assembly, the proteins form membrane associations and self-associations that ultimately result in budding of an immature virion from the infected cell. Gag precursors also function during viral assembly to selectively bind and package two plus strands of genomic RNA. Endogenous Gag proteins may have kept, lost or modified their original function during evolution.[ARBA:ARBA00024963] Publication Abstract from PubMedA significant part of the human genome consists of endogenous retroviruses sequences. Human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus, is activated and expressed in many cancers and amyotrophic lateral sclerosis and possibly contributes to the aging process. To understand the molecular architecture of endogenous retroviruses, we determined the structure of immature HERV-K from native virus-like particles (VLPs) using cryo-electron tomography and subtomogram averaging (cryoET STA). The HERV-K VLPs show a greater distance between the viral membrane and immature capsid lattice, correlating with the presence of additional peptides, SP1 and p15, between the capsid (CA) and matrix (MA) proteins compared to the other retroviruses. The resulting cryoET STA map of the immature HERV-K capsid at 3.2 A resolution shows a hexamer unit oligomerized through a 6-helix bundle which is further stabilized by a small molecule in the same way as the IP6 in immature HIV-1 capsid. The HERV-K immature CA hexamer assembles into the immature lattice via highly conserved dimmer and trimer interfaces, whose interactions were further detailed through all-atom molecular dynamics simulations and supported by mutational studies. A large conformational change mediated by the flexible linker between the N-terminal and the C-terminal domains of CA occurs between the immature and the mature HERV-K capsid protein, analogous to HIV-1. Comparison between HERV-K and other retroviral immature capsid structures reveals a highly conserved mechanism for the assembly and maturation of retroviruses across genera and evolutionary time. Molecular architecture and conservation of an immature human endogenous retrovirus.,Krebs AS, Liu HF, Zhou Y, Rey JS, Levintov L, Shen J, Howe A, Perilla JR, Bartesaghi A, Zhang P bioRxiv [Preprint]. 2023 Jun 7:2023.06.07.544027. doi: 10.1101/2023.06.07.544027. PMID:37333227[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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