Proteins and Peptides

Summary

Proteins and peptides are the workhorses of biology, underpinning structures, signals and catalysis across all forms of life. Both are polymers of amino acids linked by peptide bonds, but they differ in scale and complexity. Peptides typically consist of up to fifty residues and may function as hormones, neurotransmitters or antibiotics, whereas proteins generally exceed fifty residues, fold into defined three-dimensional architectures and perform tasks ranging from enzymatic catalysis to molecular transport and immune defence. Primary structure—the linear sequence of amino acids—dictates folding via intramolecular hydrogen bonds, hydrophobic collapse and electrostatic interactions. Secondary motifs such as α-helices and β-sheets assemble into compact tertiary folds that often oligomerise into quaternary complexes. Post-translational modifications—glycosylation, phosphorylation, acylation—further diversify function and regulation. Advances in structural biology, biophysical analysis and chemical synthesis have expanded our capacity to characterise, modify and harness these biomolecules. High-resolution techniques reveal dynamic conformational states; spectroscopic methods probe folding and interactions; and chemical ligation or ring-opening polymerisation enable the de novo creation of tailored polypeptides. Together, these approaches fuel applications in therapeutics, diagnostics, materials and the study of fundamental life processes.

Research from Nature Portfolio

Recent studies have illuminated key aspects of large protein assemblies and their manipulation. In one report, virus-neutralising potential was broadened by engineering the SARS-CoV-2 spike protein’s conserved S2 fusion subunit into a stable “S2-only” antigen. Interprotomer disulfide bonds locked the trimer in its prefusion state, and immunised mice developed broadly neutralising antibodies against diverse sarbecoviruses, laying groundwork for pan-coronavirus vaccines. Another investigation of a common-cold coronavirus spike revealed that binding of a sialoglycan primary receptor by the S1A domain triggers an allosteric cascade, inducing the S1B receptor-binding domains to open. Cryo-EM and molecular dynamics showed how glycan engagement primes the spike for protein-receptor recognition and membrane fusion, highlighting glycan-dependent regulation of viral entry. A third contribution determined the cryo-EM structure of meprin α, a secreted metalloprotease, in its zymogen and active forms. The enzyme assembles into a colossal left-handed helical filament, and oligomerisation was shown to enhance thermal and proteolytic stability. Structural comparison with meprin β identified unique active-site residues, guiding selective inhibitor design for inflammatory and cancer-related applications.

Research from all publishers

Studies beyond the Nature portfolio have advanced our understanding of peptide stereochemistry and peptide–protein synthesis. Polarized resonance Raman spectroscopy at 405 nm was applied to distinguish among heme proteins—haemoglobin, cytoglobin, neuroglobin and cytochrome c—by measuring scattering intensities in two polarisation states. Two new intensity ratios (ν7/ν15, ν15/ν3) provided sensitive discrimination in vitro and ex vivo. A comprehensive review of natural products catalogued over 130 peptide compounds containing D-amino acids, detailing biosynthetic pathways via non-ribosomal peptide synthetases and ribosomally synthesised, post-translationally modified peptides. The prevalence of D-residues in diverse taxa was correlated with altered biological activities and medicinal potential. In protein engineering, succinylation of ovalbumin with varying levels of succinic anhydride was shown to modulate secondary structure, surface charge, solubility and interfacial tension. Modified ovalbumins exhibited up to 2.7-fold increases in foaming capacity and 1.6-fold enhancements in emulsifying activity, demonstrating how targeted acylation can fine-tune functional properties for food and pharmaceutical formulations.

Proteins and Peptides publication trend

The graph below shows the total number of articles in proteins and peptides across all publications each year (not limited to Nature Index journals).

Technical terms

Peptide bond: The amide linkage between the carboxyl group of one amino acid and the amino group of another, forming the backbone of peptides and proteins.

α-Helix: A common protein secondary structure in which the polypeptide chain coils into a right-handed spiral stabilised by i→i+4 hydrogen bonds.

Prefusion conformation: The structural state of a viral fusion protein before it undergoes the large-scale refolding required for membrane merger.

Ring-opening polymerisation (ROP): A chain-growth mechanism for synthesising polypeptides from N-carboxyanhydride monomers, enabling controlled polymer lengths.

Succinylation: Covalent attachment of succinyl groups to lysine residues in proteins, altering net charge, solubility and interfacial behaviour.

References

  1. Peptides and Proteins.
  2. Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge. Nature Communications (2024).
  3. Sialoglycan binding triggers spike opening in a human coronavirus. Nature (2023).
  4. Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor. Nature Communications (2022).
  5. Polarized resonance Raman measurements for accurate heme protein differentiation. Journal of Molecular Structure (2025).
  6. Occurrence of D-amino acids in natural products. Natural Products and Bioprospecting (2023).
  7. Succinylation Modified Ovalbumin: Structural, Interfacial, and Functional Properties. Foods (2022).

About these summaries

This Nature Research Intelligence Topic summary is created with the cited references and a large language model. We take care to ground generated text with facts, and have systems in place to gain human feedback on the overall quality of the process in line with our AI principles. We strive to create accurate and useful summaries for people unfamiliar with the research topic and that supports this goal. These pages are a beta release and will be updated as we learn how best to help people gain value from a research topic summary.

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