Related Experiment Video
Updated: May 5, 2026
08:33
Nucleocapsid Annealing-Mediated Electrophoresis NAME Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors
Published on: January 19, 2015
11.8K
TRIM5α SPRY/coiled-coil interactions optimize avid retroviral capsid recognition
Marcin D Roganowicz1, Sevnur Komurlu2, Santanu Mukherjee2
1Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
Plos Pathogens
|October 18, 2017
Summary
Cellular restriction factors like TRIM5α block viral infections. This study reveals TRIM5α
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Cellular restriction factors are key components of intrinsic immunity against viral pathogens.
- TRIM5α acts as a restriction factor, inhibiting retroviruses like HIV by targeting incoming viral capsid cores.
- Efficient TRIM5α antiviral activity relies on multimerization and lattice formation for avid capsid binding, as individual SPRY domains bind weakly.
Purpose of the Study:
- To investigate the structural and functional role of the linker connecting the TRIM5α SPRY domain to the coiled-coil domain.
- To determine if TRIM5α SPRY domains are flexibly positioned or precisely spaced within the TRIM lattice for optimal avidity.
- To elucidate how linker structure influences TRIM5α's capsid recognition and antiviral efficacy.
Main Methods:
- Biochemical and biophysical experiments were employed to analyze the TRIM5α linker segment.
- Site-directed mutagenesis was used to disrupt specific interactions within the linker.
- In vitro capsid binding assays and cellular restriction assays were performed to assess mutant protein function.
Main Results:
- The linker segment adopts an α-helical fold, mediating interactions between the SPRY and coiled-coil domains.
- Mutations disrupting this helical interface impaired in vitro capsid binding and cellular restriction activity.
- These mutants retained dimerization and higher-order assembly capabilities, indicating the linker's specific role in recognition.
Conclusions:
- The linker's α-helical structure is crucial for proper positioning of TRIM5α SPRY domains.
- Tailored spacing of tethered recognition domains, facilitated by the helical linker, significantly enhances avidity during capsid recognition.
- This structural arrangement contributes substantially to TRIM5α's effectiveness as a viral restriction factor.
Related Concept Videos
01:10Retrovirus Life Cycles
43.0K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
43.0K
02:33Retroviruses
12.1K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.1K
03:18Non-LTR Retrotransposons
12.4K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
12.4K
02:28Leaky Scanning
4.5K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
4.5K
01:03Single-Strand DNA Binding Proteins
12.9K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
12.9K
01:30Inhibitors of Viral Protein Synthesis
58
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
58