4HCP

crystal structure of Burkholderia pseudomallei effector protein chbp in complex with nedd8

Summary for 4HCP

• Entry DOI: 10.2210/pdb4hcp/pdb
• Related: 4HCN
• Descriptor: Putative ATP/GTP binding protein, NEDD8, SULFATE ION, ... (5 entities in total)
• Functional Keywords: deamidase, alpha/beta/alpha fold, deamidation, nedd8/ubiquitin, bacterial cytosol, protein binding
• Biological source: Burkholderia pseudomallei; More
• Cellular location: Nucleus: Q15843
• Total number of polymer chains: 2
• Total formula weight: 37461.70

Authors

Yao, Q.,Shao, F. (deposition date: 2012-10-01, release date: 2012-11-21, Last modification date: 2024-02-28)

Primary citation

Yao, Q.,Cui, J.,Wang, J.,Li, T.,Wan, X.,Luo, T.,Gong, Y.N.,Xu, Y.,Huang, N.,Shao, F.
Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis.
Proc.Natl.Acad.Sci.USA, 109:20395-20400, 2012

PubMed Abstract: Targeting eukaryotic proteins for deamidation modification is increasingly appreciated as a general bacterial virulence mechanism. Here, we present an atomic view of how a bacterial deamidase effector, cycle-inhibiting factor homolog in Burkholderia pseudomallei (CHBP), recognizes its host targets, ubiquitin (Ub) and Ub-like neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), and catalyzes site-specific deamidation. Crystal structures of CHBP-Ub/NEDD8 complexes show that Ub and NEDD8 are similarly cradled by a large cleft in CHBP with four contacting surfaces. The pattern of Ub/NEDD8 recognition by CHBP resembles that by the E1 activation enzyme, which critically involves the Lys-11 surface in Ub/NEDD8. Close examination of the papain-like catalytic center reveals structural determinants of CHBP being an obligate glutamine deamidase. Molecular-dynamics simulation identifies Gln-31/Glu-31 of Ub/NEDD8 as one key determinant of CHBP substrate preference for NEDD8. Inspired by the idea of using the unique bacterial activity as a tool, we further discover that CHBP-catalyzed NEDD8 deamidation triggers macrophage-specific apoptosis, which predicts a previously unknown macrophage-specific proapoptotic signal that is negatively regulated by neddylation-mediated protein ubiquitination/degradation.

PubMed: 23175788
DOI: 10.1073/pnas.1210831109

Experimental method

X-RAY DIFFRACTION (2.52 Å)