5G5X
CBS domain tandem of site-2 protease from Archaeoglobus fulgidus in complex with llama Nanobody - nucleotide-bound form
Summary for 5G5X
| Entry DOI | 10.2210/pdb5g5x/pdb |
| Related | 5G5R |
| Descriptor | SITE-2 PROTEASE, NANOBODY, ADENOSINE MONOPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | hydrolase, metalloprotease, site-2 protease, regulatory domain, nucleotide-binding, cbs domain, camelid antibody, nanobody |
| Biological source | ARCHAEOGLOBUS FULGIDUS More |
| Cellular location | Cell membrane ; Multi-pass membrane protein : O29915 |
| Total number of polymer chains | 2 |
| Total formula weight | 29642.06 |
| Authors | Schacherl, M.,Baumann, U. (deposition date: 2016-06-09, release date: 2017-05-24, Last modification date: 2024-11-06) |
| Primary citation | Schacherl, M.,Gompert, M.,Pardon, E.,Lamkemeyer, T.,Steyaert, J.,Baumann, U. Crystallographic and biochemical characterization of the dimeric architecture of site-2 protease. Biochim. Biophys. Acta, 1859:1859-1871, 2017 Cited by PubMed Abstract: Regulated intramembrane proteolysis by members of the site-2 protease family (S2P) is an essential signal transduction mechanism conserved from bacteria to humans. There is some evidence that extra-membranous domains, like PDZ and CBS domains, regulate the proteolytic activity of S2Ps and that some members act as dimers. Here we report the crystal structure of the regulatory CBS domain pair of S2P from Archaeoglobus fulgidus, AfS2P, in the apo and nucleotide-bound form in complex with a specific nanobody from llama. Cross-linking and SEC-MALS analyses show for the first time the dimeric architecture of AfS2P both in the membrane and in detergent micelles. The CBS domain pair dimer (CBS module) displays an unusual head-to-tail configuration and nucleotide binding triggers no major conformational changes in the magnesium-free state. In solution, MgATP drives monomerization of the CBS module. We propose a model of the so far unknown architecture of the transmembrane domain dimer and for a regulatory mechanism of AfS2P that involves the interaction of positively charged arginine residues located at the cytoplasmic face of the transmembrane domain with the negatively charged phosphate groups of ATP moieties bound to the CBS domain pairs. Binding of MgATP could promote opening of the CBS module to allow lateral access of the globular cytoplasmic part of the substrate. PubMed: 28502790DOI: 10.1016/j.bbamem.2017.05.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
Download full validation report
