8SL1
Cryo-EM structure of PAPP-A2
Summary for 8SL1
| Entry DOI | 10.2210/pdb8sl1/pdb |
| EMDB information | 40571 |
| Descriptor | Pappalysin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total) |
| Functional Keywords | protease, zinc binding, growth factor signaling, peptide binding, hydrolase, peptide binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 175050.94 |
| Authors | Judge, R.A.,Stoll, V.S.,Eaton, D.,Hao, Q.,Bratkowski, M.A. (deposition date: 2023-04-20, release date: 2023-11-08, Last modification date: 2024-05-01) |
| Primary citation | Sridar, J.,Mafi, A.,Judge, R.A.,Xu, J.,Kong, K.A.,Wang, J.C.K.,Stoll, V.S.,Koukos, G.,Simon, R.J.,Eaton, D.,Bratkowski, M.,Hao, Q. Cryo-EM structure of human PAPP-A2 and mechanism of substrate recognition. Commun Chem, 6:234-234, 2023 Cited by PubMed Abstract: Pregnancy-Associated Plasma Protein A isoforms, PAPP-A and PAPP-A2, are metalloproteases that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate insulin-like growth factor signaling. The structures of homodimeric PAPP-A in complex with IGFBP5 anchor peptide, and inhibitor proteins STC2 and proMBP have been recently reported. Here, we present the single-particle cryo-EM structure of the monomeric, N-terminal LG, MP, and the M1 domains (with the exception of LNR1/2) of human PAPP-A2 to 3.13 Å resolution. Our structure together with functional studies provides insight into a previously reported patient mutation that inactivates PAPP-A2 in a distal region of the protein. Using a combinational approach, we suggest that PAPP-A2 recognizes IGFBP5 in a similar manner as PAPP-A and show that PAPP-A2 cleaves IGFBP5 less efficiently due to differences in the M2 domain. Overall, our studies characterize the cleavage mechanism of IGFBP5 by PAPP-A2 and shed light onto key differences with its paralog PAPP-A. PubMed: 37898658DOI: 10.1038/s42004-023-01032-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.13 Å) |
Structure validation
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