Distinct Allosteric Networks Underlie Mechanistic Speciation of ABC Transporters

Acar B., Rose J., Aykac Fas B., Ben-Tal N., Lewinson O., HALİLOĞLU T.

Structure, cilt.28, sa.6, ss.651, 2020 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.str.2020.03.014
  • Dergi Adı: Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, BIOSIS, Communication Abstracts, EMBASE, INSPEC, MEDLINE, Metadex, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.651
  • Anahtar Kelimeler: ABC transporter, allostery, ANM, ANM-LD, ATP hydrolysis, membrane protein, molecular dynamics, transport
  • Boğaziçi Üniversitesi Adresli: Evet

Özet

Long-range allosteric communication are essential to the function of molecular machines. Here, Acar et al. studied long-range communications in ABC transporters, and discovered that, despite the similar architecture of the transporters, each uses a very different communications network that is fine-tuned to its specific physiological role. ABC transporters couple the energy of ATP hydrolysis to the transmembrane transport of biomolecules. Here, we investigated the allosteric networks of three representative ABC transporters using a hybrid molecular simulations approach validated by experiments. Each of the three transporters uses a different allosteric network: in the constitutive B12 importer BtuCD, ATP binding is the main driver of allostery and docking/undocking of the substrate-binding protein (SBP) is the driven event. The allosteric signal originates at the cytoplasmic side of the membrane before propagating to the extracellular side. In the substrate-controlled maltose transporter, the SBP is the main driver of allostery, ATP binding is the driven event, and the allosteric signal propagates from the extracellular to the cytoplasmic side of the membrane. In the lipid flippase PglK, a cyclic crosstalk between ATP and substrate binding underlies allostery. These results demonstrate speciation of biological functions may arise from variations in allosteric connectivity.