3EGA

Crystal structure of Pellino2 FHA Domain at 1.8 Angstroms resolution

Summary for 3EGA

• Entry DOI: 10.2210/pdb3ega/pdb
• Related: 3EGB
• Descriptor: Protein pellino homolog 2, SULFATE ION (3 entities in total)
• Functional Keywords: pellino, fha domain, e3 ubiquitin ligase, substrate binding domain, phosphoprotein, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 29415.19

Authors

Ferguson, K.M.,Lin, C.,Schmitz, K.R. (deposition date: 2008-09-10, release date: 2008-12-23, Last modification date: 2024-11-20)

Primary citation

Lin, C.C.,Huoh, Y.S.,Schmitz, K.R.,Jensen, L.E.,Ferguson, K.M.
Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1.
Structure, 16:1806-1816, 2008

PubMed Abstract: Pellino proteins are RING E3 ubiquitin ligases involved in signaling events downstream of the Toll and interleukin-1 (IL-1) receptors, key initiators of innate immune and inflammatory responses. Pellino proteins associate with and ubiquitinate proteins in these pathways, including the interleukin-1 receptor associated kinase-1 (IRAK1). We determined the X-ray crystal structure of a Pellino2 fragment lacking only the RING domain. This structure reveals that the IRAK1-binding region of Pellino proteins consists largely of a previously unidentified forkhead-associated (FHA) domain. FHA domains are well-characterized phosphothreonine-binding modules, and this cryptic example in Pellino2 can drive interaction of this protein with phosphorylated IRAK1. The Pellino FHA domain is decorated with an unusual appendage or "wing" composed of two long inserts that lie within the FHA homology region. Delineating how this E3 ligase associates with substrates, and how these interactions are regulated by phosphorylation, is crucial for a complete understanding of Toll/IL-1 receptor signaling.

PubMed: 19081057
DOI: 10.1016/j.str.2008.09.011

Experimental method

X-RAY DIFFRACTION (1.8 Å)