Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis of complement anaphylatoxin receptor activation by an immunostimulant lead candidate.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 123, Issue 28, Page e2614459123, Year 2026
Publish date	Jul 14, 2026
Authors	Annu Dalal / Manish K Yadav / Manisankar Ganguly / Sudha Mishra / Ravi Yadav / Shachie Sinha / Nabarun Roy / Divyanshu Tiwari / Debdatta Mukherjee / Ashna Reyaz / Calvin A Dsouza / Ameesha Nigam / Nilanjana Banerjee / Xaria X Li / Richard J Clark / Trent M Woodruff / Ramanuj Banerjee / Cornelius Gati / Arun K Shukla /
PubMed Abstract	Activation of the complement cascade is a primary innate immune response mechanism to combat pathogenic infections. Complement anaphylatoxins (i.e., C3a and C5a) exert a robust inflammatory response ...Activation of the complement cascade is a primary innate immune response mechanism to combat pathogenic infections. Complement anaphylatoxins (i.e., C3a and C5a) exert a robust inflammatory response via prototypical GPCRs (i.e., C3aR and C5aR1). Several peptides derived from anaphylatoxins have shown promise as immunostimulants from therapeutic standpoint by eliciting immune response without excessive inflammation. EP67, a C5a-derived decapeptide, is the most advanced candidate with preclinical indications in antiviral and antibacterial context. Still, the molecular mechanism and the precise receptor target of EP67 remain unclear. Here, we perform a comprehensive pharmacological profiling of EP67 on the human and mouse C3aR and C5aR1 and find that it preferentially activates human C3aR in transducer-coupling assays. Subsequently, we determined four cryo-EM structures of C3aR and C5aR1 in complex with EP67, which elucidate the molecular details of its interaction with, and activation of, these receptors. Interestingly, we observe that EP67 adopts a hook-like structure and binds in the orthosteric pocket of the receptors, analogous to that of the carboxyl terminus of C3a and C5a. We employ site-directed mutagenesis studies to validate the key interactions of EP67 with these receptors and corroborate the structural observations including the engagement of a critical activation switch. Finally, we observe that EP67 induces distinct conformations of the TM7-Helix8 interface for C3aR and C5aR1, which provides a plausible explanation for its ability to preferentially activate C3aR. In summary, our study elucidates molecular insights into the interaction of EP67 with the complement anaphylatoxin receptors, and it should facilitate further optimization for therapeutic applications.
External links	Proc Natl Acad Sci U S A / PubMed:42418494 / PubMed Central
Methods	EM (single particle)
Resolution	3.07 - 3.43 Å
Structure data	62578 9kug EMDB-62578, PDB-9kug: Structure of EP67 bound to human C5aR1 in complex with Go Method: EM (single particle) / Resolution: 3.07 Å 62626 9kxs EMDB-62626, PDB-9kxs: Structure of EP67 bound mouse C5aR1 in complex with Go Method: EM (single particle) / Resolution: 3.31 Å 62651 9kz2 EMDB-62651, PDB-9kz2: Structure of EP67 bound human C3aR in complex with Go Method: EM (single particle) / Resolution: 3.43 Å 62654 9kz8 EMDB-62654, PDB-9kz8: Structure of EP67 bound mouse C3aR in complex with Go Method: EM (single particle) / Resolution: 3.3 Å
Source	homo sapiens (human) mus musculus (house mouse)
Keywords	SIGNALING PROTEIN / G protein coupled receptor / G protein / Membrane protein / Immunite system / GPCR / SIGNALING PROTEIN-IMMUNE SYSTEM complex / beta-arrestin