Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (681 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Amino Acid Sequences; Sequence, Amino Acid; Sequences, Amino Acid; Protein Structure, Primary; Primary Protein Structure; Primary Protein Structures; Protein Structures, Primary; Structure, Primary Protein.
Where it fits in the MeSH classification
- Broader topics
- Molecular Structure; Molecular Sequence Data
- Narrower topics
- Exteins; Histone Code; Immunoglobulin Variable Region; Inteins; Peptide Library; Protein Sorting Signals; Repetitive Sequences, Amino Acid
Related concepts
Research landscape
PubMed indexes 532,693 records tagged with the MeSH heading “Amino Acid Sequence” (counts retrieved 2026-10-29). 24,709 of them (4.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 231,066 records.
Reviews account for 35,420 records (6.6%) and meta-analyses for 46. Randomized controlled trials number 207 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 231,066 |
| 2000-2009 | 166,786 |
| 2010-2019 | 110,132 |
| 2020 onward | 24,709 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 35,420 | 6.6% |
| Meta-analyses | 46 | 0.0% |
| Randomized controlled trials | 207 | 0.0% |
Method: PubMed query "Amino Acid Sequence"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins | 2025 | Research article Design not recorded in structured metadata | 30 | cc by PMID 39495097 · DOI · PMC11770632 |
| Proximity-driven site-specific cyclization of phage-displayed peptides | 2024 | Research article Design not recorded in structured metadata | 17 | cc by PMID 39181880 · DOI · PMC11344848 |
| Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models | 2025 | Research article Design not recorded in structured metadata | 15 | cc by PMID 40138422 · DOI · PMC11939046 |
| Histone modification cross-talk: analytical tools and molecular mechanisms | 2026 | Review article Design not recorded in structured metadata | 4 | cc by PMID 41994991 · DOI · PMC13142947 |
A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Target class-focused drug discovery has a strong track record in pharmaceutical research, yet public domain data indicate that many members of protein families remain unliganded.
- Closing excerpt
- This study establishes a template for evaluation of protein family wide ligandability and provides an extensive resource of WDR protein biochemical and chemical tools, knowledge, and protocols to discover potential therapeutics for this highly disease-relevant, but underexplored target class.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (144 words)
Target class-focused drug discovery has a strong track record in pharmaceutical research, yet public domain data indicate that many members of protein families remain unliganded. Here we present a systematic approach to scale up the discovery and characterization of small molecule ligands for the WD40 repeat (WDR) protein family. We developed a comprehensive suite of protocols for protein production, crystallography, and biophysical, biochemical, and cellular assays. A pilot hit-finding campaign using DNA-encoded chemical library selection followed by machine learning (DEL-ML) to predict ligands from virtual libraries yielded first-in-class, drug-like ligands for 7 of the 16 WDR domains screened, thus demonstrating the broader ligandability of WDRs. This study establishes a template for evaluation of protein family wide ligandability and provides an extensive resource of WDR protein biochemical and chemical tools, knowledge, and protocols to discover potential therapeutics for this highly disease-relevant, but underexplored target class.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39495097 · DOI · PMC11770632
Proximity-driven site-specific cyclization of phage-displayed peptides [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Cyclization provides a general strategy for improving the proteolytic stability, cell membrane permeability and target binding affinity of peptides.
- Closing excerpt
- These libraries can be used for the selection of high-affinity cyclic peptide binders, as exemplified through model selections on streptavidin and the therapeutic target αvβ3.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
Cyclization provides a general strategy for improving the proteolytic stability, cell membrane permeability and target binding affinity of peptides. Insertion of a stable, non-reducible linker into a disulphide bond is a commonly used approach for cyclizing phage-displayed peptides. However, among the vast collection of cysteine reactive linkers available, few provide the selectivity required to target specific cysteine residues within the peptide in the phage display system, whilst sparing those on the phage capsid. Here, we report the development of a cyclopropenone-based proximity-driven chemical linker that can efficiently cyclize synthetic peptides and peptides fused to a phage-coat protein, and cyclize phage-displayed peptides in a site-specific manner, with no disruption to phage infectivity. Our cyclization strategy enables the construction of stable, highly diverse phage display libraries. These libraries can be used for the selection of high-affinity cyclic peptide binders, as exemplified through model selections on streptavidin and the therapeutic target αvβ3.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39181880 · DOI · PMC11344848
Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Retinal gene therapy using dual adeno-associated viral (AAV) intein vectors can be applied to genetic forms of blindness caused by mutations in genes with coding sequences that exceed single AAV cargo capacity, such as Stargardt disease (STGD1), the most common inherited macular dystrophy.
- Closing excerpt
- This bodes well for further clinical translation of dual AAV intein vectors in patients with STGD1 as well as for other blinding diseases that require the delivery of large genes.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (158 words)
Retinal gene therapy using dual adeno-associated viral (AAV) intein vectors can be applied to genetic forms of blindness caused by mutations in genes with coding sequences that exceed single AAV cargo capacity, such as Stargardt disease (STGD1), the most common inherited macular dystrophy. In view of clinical translation of dual AAV intein vectors, here we set to evaluate both the efficiency and safety of their subretinal administration in relevant large animal models. Accordingly, we have developed the first pig model of STGD1, which we found to accumulate lipofuscin similarly to patients. This accumulation is significantly reduced upon subretinal administration of dual AAV intein vectors whose safety and pharmacodynamics we then tested in nonhuman primates, which showed modest and reversible inflammation as well as high levels of photoreceptor transduction. This bodes well for further clinical translation of dual AAV intein vectors in patients with STGD1 as well as for other blinding diseases that require the delivery of large genes.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40138422 · DOI · PMC11939046
Histone modification cross-talk: analytical tools and molecular mechanisms [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Chromatin function emerges from combinatorial patterns of histone post-translational modifications (PTMs) that are read, written, and erased by dedicated enzymes.
- Closing excerpt
- These examples illustrate the principle of epigenetic cross-talk, namely, that specific combinatorial PTMs can affect enzymes and alter local biochemistry.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (230 words)
Chromatin function emerges from combinatorial patterns of histone post-translational modifications (PTMs) that are read, written, and erased by dedicated enzymes. Over the past 30 years, increasing evidence suggests that specific histone PTMs or combinations of PTMs influence one another, constituting epigenetic cross-talk that shapes chromatin structure, protein-protein interactions, and catalytic efficiency of nucleosome-targeting enzymes. Here, we summarize mechanistic and methodological advances that enable rigorous interrogation of histone PTM interplay. We highlight selected nucleosome engineering strategies that build precisely modified substrates to test in vitro, proteomic pipelines that preserve combinatorial information, and omics technology that can globally profile integrated chromatin regulatory events in cells and tissues. Furthermore, we survey multivalent reader modules and engineered biosensors that report combinatorial marks in nucleosomes and living cells. Representative case studies illustrate how defined PTMs modulate catalytic parameters of writer and eraser complexes, including lysine methyltransferases, demethylases, acetyltransferases, and deacetylases, focusing on cross-talk with histone H3 N-terminal tail marks. These include the role of H3K9me2/3 and K14ac in directing propagation of H3K9me3, the role of H3K4me1/2 and K14ac in slowing H3K4 demethylation, the role of H3K4me2/3 in directing H3K9 acetylation, and the role of H3K36 methylation in directing deacetylation of H3 and H4. The substrates for these case studies include both mononucleosomes and nucleosome arrays. These examples illustrate the principle of epigenetic cross-talk, namely, that specific combinatorial PTMs can affect enzymes and alter local biochemistry.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41994991 · DOI · PMC13142947
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Writing, erasing and reading histone lysine methylations [5]
- Research article EZH2: a novel target for cancer treatment [6]
- Research article Histone Modifications and Cancer [7]
- Research article The interplay of histone modifications - writers that read [8]
- Research article Types of nuclear localization signals and mechanisms of protein import into the nucleus [9]
- Research article Protein export through the bacterial Sec pathway [10]
References
- Ackloo S, Li F, Szewczyk M, Seitova A, Loppnau P, Zeng H, et al.. A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins. . 2025. PMID 39495097 · DOI · PMC11770632
- Brown L, Vidal AV, Dias AL, Rodrigues T, Sigurdardottir A, Journeaux T, et al.. Proximity-driven site-specific cyclization of phage-displayed peptides. . 2024. PMID 39181880 · DOI · PMC11344848
- Ferla R, Pugni E, Lupo M, Tiberi P, Fioretto F, Perota A, et al.. Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models. . 2025. PMID 40138422 · DOI · PMC11939046
- Jiang J, DuBois-Coyne S, Nam E, Whedon SD, Lee K, Cole PA. Histone modification cross-talk: analytical tools and molecular mechanisms. . 2026. PMID 41994991 · DOI · PMC13142947
- Hyun K, Jeon J, Park K, Kim J. Writing, erasing and reading histone lysine methylations. Exp Mol Med. 2017. PMID 28450737 · DOI · PMC6130214
- Duan R, Du W, Guo W. EZH2: a novel target for cancer treatment. J Hematol Oncol. 2020. PMID 32723346 · DOI · PMC7385862
- Audia JE, Campbell RM. Histone Modifications and Cancer. Cold Spring Harb Perspect Biol. 2016. PMID 27037415 · DOI · PMC4817802
- Zhang T, Cooper S, Brockdorff N. The interplay of histone modifications - writers that read. EMBO Rep. 2015. PMID 26474904 · DOI · PMC4641500
- Lu J, Wu T, Zhang B, Liu S, Song W, Qiao J, et al.. Types of nuclear localization signals and mechanisms of protein import into the nucleus. Cell Commun Signal. 2021. PMID 34022911 · DOI · PMC8140498
- Tsirigotaki A, De Geyter J, Šoštaric N, Economou A, Karamanou S. Protein export through the bacterial Sec pathway. Nat Rev Microbiol. 2017. PMID 27890920 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.