Medical Biochemistry - Proteins and Peptides

Proteins and peptides are the primary functional polymers of medical biochemistry, directing virtually all cellular processes through their structural diversity, catalytic activities and signalling roles. Built from the 20 canonical amino acids linked by peptide bonds, these biopolymers adopt defined primary sequences that fold into local secondary elements—α-helices, β-sheets, turns—and assemble into tertiary and quaternary architectures. Their three-dimensional shapes and dynamic fluctuations underpin enzyme catalysis, receptor–ligand recognition, immune surveillance and intercellular communication. Proteolytic peptides, for example hormones or neuropeptides, modulate metabolism, growth and neurological function at nanomolar concentrations, while larger globular proteins perform bulk transport, structural support and macromolecular assembly. Dysregulation or misfolding of proteins and peptides lies at the heart of many human pathologies, including enzyme-deficiency syndromes, neurodegeneration, cancer and metabolic disorders. Advances in recombinant expression, peptide synthesis and chemical modification have ushered in an era of protein-based therapeutics—replacement enzymes, monoclonal antibodies, hormone analogues and peptide agonists—that complement small-molecule drugs. Contemporary research in medical biochemistry focuses on the molecular mechanisms of protein folding, quality control and post-translational regulation, the design of peptide ligands with high specificity and favourable pharmacokinetics, and the development of analytical tools to characterise structure–function relationships in health and disease.

Research from Nature Portfolio

Recent studies have disentangled how cells maintain endoplasmic reticulum (ER) proteostasis under physiological and stress conditions. One investigation delineated the interplay between ER-associated degradation (ERAD) and selective ER autophagy (ER-phagy) in adipocytes. When the SEL1L–HRD1 ubiquitin ligase complex fails to clear misfolded luminal proteins, ER fragments enriched in chaperones and misassembled clients are sequestered into specialised assemblies termed CERFs, which are then eliminated via autophagy. This sequential hierarchy highlights how redox conditions and substrate composition dictate phase-separation events that safeguard the secretory pathway in vivo. In a complementary work, cryo-EM and NMR spectroscopy were combined to visualise the ATP-driven conformational cycle of the hexameric AAA+ ATPase p97 at near-atomic resolution. By capturing the elusive ADP·Pi intermediate, researchers revealed how phosphate trapping triggers coordinated allosteric rearrangements that couple ATP hydrolysis to mechanical substrate extraction. These insights deepen our mechanistic understanding of both ER protein disposal and the segregase functions vital for proteome integrity.

Medical Biochemistry - Proteins and Peptides publication trend

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

Technical terms

Proteostasis: The homeostatic network of protein synthesis, folding, trafficking and degradation that preserves functional proteomes.

ER-associated degradation (ERAD): A pathway whereby misfolded ER lumenal or membrane proteins are ubiquitinated, retrotranslocated to the cytosol and degraded by the proteasome.

ER-phagy: Selective autophagy of ER fragments containing insoluble or aggregated clients, serving as a backup route for ER quality control.

AAA+ ATPase: A family of ATP-hydrolysing enzymes that exert mechanical forces to remodel, disaggregate or extract protein substrates from macromolecular assemblies.

Chaperone: A protein that assists folding, stabilises intermediates or prevents aggregation without being part of the final structure.

Adaptor: A factor that connects specific substrates to degradation or remodelling machines, such as ubiquitin ligases or AAA+ ATPases.

References

1. Peptides and Proteins.
2. The mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes. Nature Communications (2023).
3. Characterizing ATP processing by the AAA+ protein p97 at the atomic level. Nature Chemistry (2024).
4. Mechanism of orphan subunit recognition during assembly quality control. Cell (2023).
5. Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases. Molecular Neurodegeneration (2023).