Related Experiment Video
Updated: Jun 29, 2025
10:34
Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
4.1K
AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Spike Protein Variants
Muhammad Asif Ali1, Gustavo Caetano-Anollés1
1Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biology
|March 27, 2024
Summary
Deep learning models reveal significant structural changes in SARS-CoV-2 S-proteins, including N-terminal and receptor-binding domains. Haplotypes influence these changes, impacting viral evolution and aiding future vaccine development.
Area of Science:
- Structural biology
- Virology
- Computational biology
Background:
- Experimental determination of SARS-CoV-2 protein structures is slow, hindering drug and vaccine development.
- Deep learning models like AlphaFold2 offer rapid, high-resolution atomic structure prediction.
- Previous studies overlooked the impact of viral haplotypes on protein structure, focusing only on variant constellations.
Purpose of the Study:
- To conduct a comparative structural analysis of SARS-CoV-2 S-proteins from major Variants of Concern (VOCs) and their associated haplotypes.
- To identify key molecular regions and patterns of structural change influenced by viral evolution.
- To understand the role of structural modifications in viral seasonal behavior and environmental sensing.
Main Methods:
- Comparative structural analysis of S-proteins from major SARS-CoV-2 VOCs and haplotypes.
- Utilizing deep learning tools for atomic structure modeling.
- Analyzing structural changes, particularly in the S1 subunit, N-terminal domain (NTD), and receptor-binding domain (RBD).
Main Results:
- The S1 subunit, especially the NTD and RBD, exhibited the most significant structural alterations.
- Structural changes in the NTD were complex, involving sub-structure alterations beyond simple spatial translations.
- A pattern of structural recruitment was observed: early VOCs (Alpha, Delta) antagonistically suppressed haplotype-induced changes, while Omicron synergistically amplified them.
- Haplotypes affecting the NTD's galectin-like structure were crucial for viral seasonal behavior.
Conclusions:
- The study provides a comprehensive view of the SARS-CoV-2 S-protein evolutionary landscape.
- Identified structural changes and recruitment patterns can predict critical regions in future variants and haplotypes.
- Findings will aid in developing more effective vaccines and therapeutics against evolving coronaviruses.
Keywords:
AlphaFoldCOVID-19evolutionary pressurehaplotypesmutationpandemicprotein structurerecruitmentspike proteinvariant of concernMore Related Videos
22:10Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit
Published on: June 28, 2013
13.3K
10:50Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
9.6K
Related Concept Videos
01:22Protein Folding
118.0K
Overview
118.0K
01:25Nucleic Acid Structure
6.1K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
DNA Structure
DNA...
6.1K
02:21Globular and Fibrous Proteins
43.7K
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
43.7K
02:28Leaky Scanning
5.1K
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...
5.1K
02:15Protein and Protein Structure
79.5K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
79.5K
02:47Protein Families
15.3K
Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism. Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members. If these new proteins contain similar amino acids in key...
15.3K