Insights into varicella-zoster virus assembly from the B-and C-capsid at near-atomic resolution structures

Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.

谷氨酸脱氢酶与几种肿瘤的关系

大多数生物体中都含有谷氨酸脱氢酶(Glutamate dehydrogenase, GDH)(E.C. 1.4.1.2–1.4.1.4)。在真核生物中,该酶主要存在于线粒体中,并在氮和碳的代谢以及信号通路中起着至关重要的作用。研究发现谷氨酸脱氢酶与肿瘤发生及发展有一定的关系,对于肿瘤研究具有一定意义,但是关于其与人类肿瘤的关系方面的综述很少见。文中对谷氨酸脱氢酶与乳腺癌、胶质瘤、结直肠癌以及卵巢癌等的关系进行了归纳和总结,希望可以为相关研究提供帮助。

Architecture of the herpesvirus genomepackaging complex and implications for DNA translocation

Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs.Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown.We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP·BeF3-bound states.Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins,pUL28 and pUL33-unlike bacteriophage terminases.Distal to the nuclease domains,six ATPase domains form a central channel with conserved basicpatches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation.Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode.Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.

Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design

Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold worldwide.The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune system.These key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been determined.These structures shed light on the determinants of drug specificity.Here we describe the structures of HRV-C153C in free and inhibitor-bound forms.The volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C protease.Rupintrivir assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral inhibitors.Analysis of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.