{
  "abstract": "Visualizing the structures of small proteins and complexes has been a longstanding challenge in single-particle cryo-electron microscopy (cryo-EM). Some of these targets have been successfully resolved by binding to antibody fragments (Fabs) or fusing with external scaffolds to increase their size. Recent advances in conventional single-particle techniques have enabled the determination of an increasing number of structures smaller than 100 kDa, achieving resolutions relevant to drug research. Compared to X-ray crystallography, cryo-EM preserves the near-native states of biomolecules, can resolve structural heterogeneity, and has the potential to apply to a wide range of targets. In this work, we demonstrate that the alignment and reconstruction of small macromolecular complexes can be improved using high-resolution structures as priors, combined with 2D template matching. Using this method, we reconstructed a previously intractable ∼43 kDa protein kinase and improved the density of its ligand-binding site. Our theoretical analysis predicts that this method can further extend single-particle cryo-EM to important drug-binding complexes well below 50 kDa.",
  "abstract_shown": true,
  "affiliations": [
    "RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, United States.",
    "Howard Hughes Medical Institute, Worcester, United States.",
    "Department of Biochemistry, University of Wisconsin-Madison, Madison, United States.",
    "Morgridge Institute for Research, Madison, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kexin Zhang",
      "orcid": "0000-0002-3273-2797"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Timothy Grant",
      "orcid": "0000-0002-4855-8703"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nikolaus Grigorieff",
      "orcid": "0000-0002-1506-909X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5jrea3k3fnnw7.bib",
  "cited_by": 0,
  "doi": "10.7554/elife.109790",
  "fulltext_url": "https://europepmc.org/articles/PMC13707379",
  "id": "5jrea3k3fnnw7",
  "issns": [
    "2050-084X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42930231",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1315|Advanced Electron Microscopy Techniques and Applications"
    ]
  ],
  "openalex": "W7124827218",
  "pdf_url": "https://europepmc.org/articles/PMC13707379?pdf=render",
  "pmcid": "PMC13707379",
  "pmid": "42930231",
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5jrea3k3fnnw7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42930231",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42930231"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1315|Advanced Electron Microscopy Techniques and Applications",
      "subfield": "structural-biology"
    }
  ],
  "title": "Improved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching.",
  "title_text": "Improved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/5jrea3k3fnnw7",
  "venue": "ELife",
  "versions": []
}