{
  "abstract": "We characterized the structural determinants of phospholamban (PLB) and sarcolipin (SLN) self-assembly, using experimental and computational assays. PLB and SLN are transmembrane peptides that regulate contractility via phosphorylation-dependent regulation of the sarcoplasmic reticulum Ca²⁺-ATPase (SERCA). The physiological role of PLB and SLN has been proposed to be important as a reservoir for fine-tuning SERCA activity and to act as ion-selective channels. Structural studies of PLB and SLN transmembrane domains have indicated stabilization of higher-order oligomers by leucine/isoleucine zippers in a heptad-repeat motif (a-g residue positions), requiring residue C41. Here we have modeled and tested the additional residues responsible for self-assembly using alanine replacement. We demonstrate that PLB e-position residues in the cleft between subunits contribute to self-association affinity and stoichiometry. For SLN, we identified two residues (V14, L21) and a novel heptad repeat (a-position) that contribute to self-association affinity and stoichiometry. This is in addition to the d-position that we previously identified for SLN oligomerization. Our molecular models demonstrate stable hexamer assemblies, but without the likelihood of a hydrated pore. We propose that PLB and SLN populate a distribution of oligomeric forms in sarcoplasmic reticulum membranes (monomer through pentamer and hexamer) and suggest that pore formation requires increased toroidal stoichiometry.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bengt Svensson",
      "orcid": "0000-0003-3932-2376"
    },
    {
      "affs": [
        0
      ],
      "name": "Joseph M Autry",
      "orcid": "0000-0002-1144-725X"
    },
    {
      "affs": [
        0
      ],
      "name": "John E Rubin"
    },
    {
      "affs": [
        0
      ],
      "name": "Robyn T Rebbeck",
      "orcid": "0000-0003-3840-2286"
    },
    {
      "affs": [
        0
      ],
      "name": "David D Thomas",
      "orcid": "0000-0002-8822-2040"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/64eyrnp2hrnhe.bib",
  "cited_by": 0,
  "doi": "10.3390/membranes16100323",
  "fulltext_url": "https://europepmc.org/articles/PMC13707140",
  "id": "64eyrnp2hrnhe",
  "issns": [
    "2077-0375"
  ],
  "landing_url": "https://europepmc.org/article/MED/42931001",
  "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",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7214610812",
  "pdf_url": "https://europepmc.org/articles/PMC13707140?pdf=render",
  "pmcid": "PMC13707140",
  "pmid": "42931001",
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/64eyrnp2hrnhe.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42931001",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42931001"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Phospholamban and Sarcolipin Share Similar Transmembrane Zipper Motifs That Control Self-Association Affinity and Homo-Oligomer Stoichiometry.",
  "title_text": "Phospholamban and Sarcolipin Share Similar Transmembrane Zipper Motifs That Control Self-Association Affinity and Homo-Oligomer Stoichiometry.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/64eyrnp2hrnhe",
  "venue": "Membranes",
  "versions": []
}