7sk5 › Citations

Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.
<div class='caption-title'>Overview of the CID25-ACKR3·CXCL12-CID24 complex (PDB entry 7SK3).</div>
<div class='caption-title'>Atypical binding mode of CXCL12 on ACKR3.</div>
Yen YC, Schafer CT, Gustavsson M, Eberle SA, Dominik PK, Deneka D, Zhang P, Schall TJ, Kossiakoff AA, Tesmer JJG, Handel TM
OpenAccess logo Sci Adv 8 eabn8063 (2022)
Related entries: 7sk3, 7sk4, 7sk6, 7sk7, 7sk8, 7sk9

Cited: 27 times
EuropePMC logo PMID: 35857509

Abstract

Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward β-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs.

Articles - 7sk5 mentioned but not cited (4)

  1. Regulation of polymerase II transcription by 7SK snRNA: two distinct RNA elements direct P-TEFb and HEXIM1 binding. Egloff S, Van Herreweghe E, Kiss T. Mol Cell Biol 26 630-642 (2006)
  2. Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias. Yen YC, Schafer CT, Gustavsson M, Eberle SA, Dominik PK, Deneka D, Zhang P, Schall TJ, Kossiakoff AA, Tesmer JJG, Handel TM. Sci Adv 8 eabn8063 (2022)
  3. Structural insights into the activation and inhibition of CXC chemokine receptor 3. Jiao H, Pang B, Liu A, Chen Q, Pan Q, Wang X, Xu Y, Chiang YC, Ren R, Hu H. Nat Struct Mol Biol 31 610-620 (2024)
  4. Structural basis for selectivity and antagonism in extracellular GPCR-nanobodies. Schlimgen RR, Peterson FC, Heukers R, Smit MJ, McCorvy JD, Volkman BF. Nat Commun 15 4611 (2024)


Reviews citing this publication (9)

  1. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention. Cambier S, Gouwy M, Proost P. Cell Mol Immunol 20 217-251 (2023)
  2. The multifunctional protein HMGB1: 50 years of discovery. Tang D, Kang R, Zeh HJ, Lotze MT. Nat Rev Immunol 23 824-841 (2023)
  3. G protein-coupled receptor interactions with arrestins and GPCR kinases: The unresolved issue of signal bias. Chen Q, Tesmer JJG. J Biol Chem 298 102279 (2022)
  4. Atypical chemokine receptors: emerging therapeutic targets in cancer. Torphy RJ, Yee EJ, Schulick RD, Zhu Y. Trends Pharmacol Sci 43 1085-1097 (2022)
  5. Atypical chemokine receptors in the immune system. Comerford I, McColl SR. Nat Rev Immunol 24 753-769 (2024)
  6. Development of tolerance to chemokine receptor antagonists: current paradigms and the need for further investigation. Grudzien P, Neufeld H, Ebe Eyenga M, Gaponenko V. Front Immunol 14 1184014 (2023)
  7. Intracellular VHHs to monitor and modulate GPCR signaling. Raynaud P, Gauthier C, Jugnarain V, Jean-Alphonse F, Reiter E, Bruneau G, Crépieux P. Front Endocrinol (Lausanne) 13 1048601 (2022)
  8. C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4 signaling axis in cancer and the development of chemotherapeutic molecules. Yen JH, Chang CC, Hsu HJ, Yang CH, Mani H, Liou JW. Tzu Chi Med J 36 231-239 (2024)
  9. The Impact of Nanobodies on G Protein-Coupled Receptor Structural Biology and Their Potential as Therapeutic Agents. Salom D, Wu A, Liu CC, Palczewski K. Mol Pharmacol 106 155-163 (2024)

Articles citing this publication (14)

  1. Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system. Sarma P, Carino CMC, Seetharama D, Pandey S, Dwivedi-Agnihotri H, Rui X, Cao Y, Kawakami K, Kumari P, Chen YC, Luker KE, Yadav PN, Luker GD, Laporte SA, Chen X, Inoue A, Shukla AK. Nat Commun 14 4808 (2023)
  2. Atypical Chemokine Receptor 3 "Senses" CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation. Schafer CT, Chen Q, Tesmer JJG, Handel TM. Mol Pharmacol 104 174-186 (2023)
  3. Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors. Maharana J, Sano FK, Sarma P, Yadav MK, Duan L, Stepniewski TM, Chaturvedi M, Ranjan A, Singh V, Saha S, Mahajan G, Chami M, Shihoya W, Selent J, Chung KY, Banerjee R, Nureki O, Shukla AK. Science 383 101-108 (2024)
  4. Proteolytic inactivation of CXCL12 in the lungs and circulation of COVID-19 patients. Cambier S, Beretta F, Pörtner N, Metzemaekers M, de Carvalho AC, Martens E, Kaes J, Aelbrecht C, Jacobs C, Van Mol P, Wauters E, Meersseman P, Hermans G, Marques RE, Vanaudenaerde B, Vos R, Wauters J, Gouwy M, Proost P. Cell Mol Life Sci 80 234 (2023)
  5. Structural and Phylogenetic Analysis of CXCR4 Protein Reveals New Insights into Its Role in Emerging and Re-Emerging Diseases in Mammals. Naheed F, Mumtaz R, Shabbir S, Jamil A, Asif AR, Rahman A, Ahmad HI, Essa M, Akhtar H, Mahmoud SF, Alghamdi FO, Amari HAA, Chen J. Vaccines (Basel) 11 671 (2023)
  6. Conformational dynamics underlying atypical chemokine receptor 3 activation. Otun O, Aljamous C, Del Nero E, Arimont-Segura M, Bosma R, Zarzycka B, Girbau T, Leyrat C, de Graaf C, Leurs R, Durroux T, Granier S, Cong X, Bechara C. Proc Natl Acad Sci U S A 121 e2404000121 (2024)
  7. Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3). Dekkers S, Comez D, Karsai N, Arimont-Segura M, Canals M, Caspar B, de Graaf C, Kilpatrick LE, Leurs R, Kellam B, Hill SJ, Briddon SJ, Stocks MJ. ACS Med Chem Lett 15 143-148 (2024)
  8. Structural insights into CXCR4 modulation and oligomerization. Saotome K, McGoldrick LL, Ho JH, Ramlall TF, Shah S, Moore MJ, Kim JH, Leidich R, Olson WC, Franklin MC. Nat Struct Mol Biol (2024)
  9. Structural snapshot of a β-arrestin-biased receptor. Sarma P, Banerjee R, Shukla AK. Trends Pharmacol Sci 44 1-3 (2023)
  10. Heterogeneous expression of the atypical chemokine receptor ACKR3 in glioblastoma patient-derived tissue samples and cell cultures. Isci D, Kuppens A, Scalisi J, Cokaiko J, D'Uonnolo G, Wantz M, Szpakowska M, Chevigné A, Rogister B, Neirinckx V. Sci Rep 14 21925 (2024)
  11. Molecular mechanism of distinct chemokine engagement and functional divergence of the human Duffy antigen receptor. Saha S, Khanppnavar B, Maharana J, Kim H, Carino CMC, Daly C, Houston S, Sharma S, Zaidi N, Dalal A, Mishra S, Ganguly M, Tiwari D, Kumari P, Jhingan GD, Yadav PN, Plouffe B, Inoue A, Chung KY, Banerjee R, Korkhov VM, Shukla AK. Cell 187 4751-4769.e25 (2024)
  12. Multiplex Detection of Fluorescent Chemokine Binding to CXC Chemokine Receptors by NanoBRET. Adamska JM, Leftheriotis S, Bosma R, Vischer HF, Leurs R. Int J Mol Sci 25 5018 (2024)
  13. Resonating with the signaling bias of CXCR7. Sarma P, Shukla AK. Mol Cell 82 3318-3320 (2022)
  14. Structural Space of the Duffy Antigen/Receptor for Chemokines' Intrinsically Disordered Ectodomain 1 Explored by Temperature Replica-Exchange Molecular Dynamics Simulations. Kranjc A, Narwani TJ, Abby SS, de Brevern AG. Int J Mol Sci 24 13280 (2023)


Quick links