5Z7A

Crystal structure of NDP52 SKICH region

Summary for 5Z7A

• Entry DOI: 10.2210/pdb5z7a/pdb
• Descriptor: Calcium-binding and coiled-coil domain-containing protein 2, SULFATE ION, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (5 entities in total)
• Functional Keywords: ndp52, skich, autophagy receptor, selective autophagy, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 30554.55

Authors

Pan, L.F.,Fu, T.,Liu, J.P.,Xie, X.Q. (deposition date: 2018-01-27, release date: 2019-01-02, Last modification date: 2023-11-22)

Primary citation

Fu, T.,Liu, J.,Wang, Y.,Xie, X.,Hu, S.,Pan, L.
Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1
Proc. Natl. Acad. Sci. U.S.A., 115:E11651-E11660, 2018

PubMed Abstract: NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy. The autophagic functions of NDP52 and TAX1BP1 are regulated by TANK-binding kinase 1 (TBK1), which may associate with them through the adaptor NAP1. However, the molecular mechanism governing the interactions of NAP1 with NDP52 and TAX1BP1, as well as the effects induced by TBK1-mediated phosphorylation of NDP52 and TAX1BP1, remains elusive. Here, we report the atomic structures of the SKICH regions of NDP52 and TAX1BP1 in complex with NAP1, which not only uncover the mechanistic bases underpinning the specific interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1 but also reveal the binding mode of a SKICH domain. Moreover, we uncovered that the SKICH domains of NDP52 and TAX1BP1 share a general binding mode to interact with NAP1. Finally, we also evaluated the currently known TBK1-mediated phosphorylation sites in the SKICH domains of NDP52 and TAX1BP1 on the basis of their interactions with NAP1. In all, our findings provide mechanistic insights into the interactions of NAP1 with NDP52 and TAX1BP1, and are valuable for further understanding the functions of these proteins in selective autophagy.

PubMed: 30459273
DOI: 10.1073/pnas.1811421115

Experimental method

X-RAY DIFFRACTION (2.38 Å)