Fig. 4: Cryo-EM structure of the HKU5 RBD in complex with P. abramus ACE2.
From: HKU5 bat merbecoviruses engage bat and mink ACE2 as entry receptors
a Cryo-EM density (left) and refined model (right) for the HKU5RBD in complex with P. abramus ACE2. The ACE2 is colored in green, and the RBD is colored in orange. b Footprints of the P. abramus ACE2 and HKU5RBD complex are shown in open-book view. c Interactions at the interface. The complex is shown in the 45-degree rotated view compared to the orientation in (a). The interactions are divided into two patches. HKU5RBD tyrosines provide more than 500 Å2 binding surface for the P. abramus ACE2. Tyrosines in patch 1 form extensive interactions with a helical region on ACE2 that spans P324ACE2, R328ACE2, and D329ACE2. Patch 2 interactions involve hydrogen bonding between HKU5RBD tyrosines and A385ACE2, glycan 387ACE2, K352ACE2, as well salt bridge between E510RBD and K352ACE2. The Y517RBD is wedged between I92ACE2 and I93ACE2 and interacts with R26ACE2 and D90ACE2. d Comparison of binding modes of the RBDs of HKU5, SARS-CoV-2, NeoCoV and PDF-2180 CoV to ACE2. All structures (PDB ID: 6M0J, 7WPO, and 7WPZ) were superimposed onto the HKU5RBD-bound to P. abramus ACE2. Footprints of the HKU5RBD, SARS-CoV-2RBD, PDF-2180RBD, and NeoCoVRBD are marked on the surface representation of P. abramus ACE2 and colored in the same color as their respective RBDs in the left panel. A zoomed-in view is shown to the lower right to compare the binding difference of HKU5RBD and SARS-CoV-2RBD relative to the ACE2 α1 helix. e, f Structural conservation map of the RBDs from the spike proteins of MERS-CoV, PDF-2180, and HKU5. Sequence conservation between HKU5, NeoCoV, PDF-2180, and MERS-CoV is mapped along the HKU5-P. abramus ACE2 binding footprint (outlined in black) on the HKU5 RBD (burnt orange) e. Pairwise sequence conservation between HKU5 and the RBD of NeoCoV (sand), PDF-2180 (pink), or MERS-CoV (salmon) is mapped to their respective binding footprints (outlined in black) f. Amino acid sequence with conservation colored blue and divergence red.
