The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3, referred to as A3) proteins are cellular cytidine deaminases that potently restrict retrovirus replication. However, HIV-1 viral infectivity factor (Vif) counteracts the antiviral activity of most A3 proteins by targeting them for proteasomal degradation. To date, the structure of an A3 protein containing a Vif-binding interface has not been solved. Here, we report a high-resolution crystal structure of APOBEC3C and identify the HIV-1 Vif-interaction interface. Extensive structure-guided mutagenesis revealed the role of a shallow cavity composed of hydrophobic or negatively charged residues between the α2 and α3 helices. This region is distant from the DPD motif (residues 128-130) of APOBEC3G that participates in HIV-1 Vif interaction. These findings provide insight into Vif-A3 interactions and could lead to the development of new pharmacologic anti-HIV-1 compounds.
APOBEC3H (A3H) is a mammal-specific cytidine deaminase that potently restricts the replication of retroviruses. Primate A3Hs are known to exert key selective pressures against the cross-species transmission of primate immunodeficiency viruses from chimpanzees to humans. Despite recent advances, the molecular structures underlying the functional mechanisms of primate A3Hs have not been fully understood. Here, we reveal the 2.20-Å crystal structure of the chimpanzee A3H (cpzA3H) dimer bound to a short double-stranded RNA (dsRNA), which appears to be similar to two recently reported structures of pig-tailed macaque A3H and human A3H. In the structure, the dsRNA-binding interface forms a specialized architecture with unique features. The analysis of the dsRNA nucleotides in the cpzA3H complex revealed the GC-rich palindrome-like sequence preference for dsRNA interaction, which is largely determined by arginine residues in loop 1. In cells, alterations of the cpzA3H residues critical for the dsRNA interaction severely reduce intracellular protein stability due to proteasomal degradation. This suggests that cpzA3H stability is regulated by the dsRNA-mediated dimerization as well as by unknown cellular machinery through proteasomal degradation in cells. Taken together, these findings highlight unique structural features of primate A3Hs that are important to further understand their cellular functions and regulation.
This paper presents a parallel processing scheme and software architecture of SMASH, a parallel processing system for supporting a wide variety of database applications. The main feature of this system is functional programming concepts applied to define new database operations and data types and exploit parallelisms inherent in an arbitrary set of database operations. In this paper, we present a primitive set(SMASH primitive set) of the software architecture that defines an abstract machine interface between high level database languages and general purpose hardware systems for parallel processing. The primitive set is used to implement functional computation systems for executing arbitrary database operations in parallel.We have proposed a stream-oriented parallel processing scheme for relational database operations. In this paper, this scheme is extended to support more complex database operations which deal with complex data structures. Furthermore, several experimental results of parallel processing for database operations are shown to clarify feasibility of our proposed architecture.
SAMTK: Scalable Adaptive Multicast Toolkit is a toolkit to bridge the gap between network researchers and application developers in the field of multi-point communication. SAMTK includes a Qt based GUI that ensures a single source multi-platform use (Linux, FreeBSD, Windows and MacOS). It provides interfaces for network plugins used by one-to-many network sockets and a simple application programming interface for application developers to develop multi-point communication applications quite easily. ALR: Application Layer Router is a router which parses UDP packets and does a lookup in itsinternal forwarding table to duplicate and deliver the packets to multiple destinations. It provides NAT traversal function by using a singe UDP port both for session registration and packet delivery. The demo shows the feasibility of NAT free 3D video conferencing using Application Layer Router and the ease of development of video conferencing applications using SAMTK.
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