{
  "abstract": "The rapid increase in experimentally resolved G protein-coupled receptor (GPCR)–biologic complexes has substantially improved our understanding of the molecular basis of receptor recognition and modulation. However, despite the growing number of available structures, a comparative framework integrating the major GPCR classes is still lacking. In this review, we analysed experimentally resolved GPCR–biologic complexes across receptor Classes A, B, C, and F to identify the structural principles governing biologic recognition. Our analysis shows that the architecture of each GPCR class shapes distinct recognition paradigms, while two interdependent structural variables emerge across the superfamily: the accessibility and organization of receptor surfaces and the conformational states associated with these regions. Class A receptors primarily expose compact extracellular surfaces, Class B receptors exploit large extracellular domains that support modular ligand recognition, whereas Class C and Class F receptors rely on structured extracellular domains (Venus Flytrap and cysteine-rich domains, respectively) that enable conformational selection and allosteric regulation. Together, these observations establish a structural framework linking receptor accessibility and conformational dynamics to biologic recognition and pharmacological modulation. This framework provides a conceptual foundation for the rational design of next-generation GPCR-targeted biologics with improved selectivity, efficacy, and functional precision.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano, 49, I-80131 Naples, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bianca Fiorillo",
      "orcid": "0000-0002-3025-5157"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessandra Guarracino"
    },
    {
      "affs": [
        0
      ],
      "name": "Oriana Vitale"
    },
    {
      "affs": [
        0
      ],
      "name": "Federica Moraca",
      "orcid": "0000-0002-1077-1971"
    },
    {
      "affs": [
        0
      ],
      "name": "Bruno Catalanotti",
      "orcid": "0000-0002-7532-6959"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fat4dh9t1n8bd.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15211958",
  "fulltext_url": null,
  "id": "fat4dh9t1n8bd",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/21/1958",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7224125985",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/fat4dh9t1n8bd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15211958",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/21/1958"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structural Determinants of Biologic Recognition Across GPCR Classes",
  "title_text": "Structural Determinants of Biologic Recognition Across GPCR Classes",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:02Z",
  "url": "https://research.draconitic.com/paper/fat4dh9t1n8bd",
  "venue": "Cells",
  "versions": []
}