2QNJ

Kinase and Ubiquitin-associated domains of MARK3/Par-1

2QNJ の概要

• エントリーDOI: 10.2210/pdb2qnj/pdb
• 分子名称: MAP/microtubule affinity-regulating kinase 3 (2 entities in total)
• 機能のキーワード: serine/threonine protein kinase, ubiquitin-associated domain, mark, par-1, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane ; Peripheral membrane protein : P27448
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75337.13

構造登録者

Murphy, J.M.,Ceccarelli, D.F.J.,Sicheri, F.,Pawson, T. (登録日: 2007-07-18, 公開日: 2007-09-04, 最終更新日: 2024-10-30)

主引用文献

Murphy, J.M.,Korzhnev, D.M.,Ceccarelli, D.F.,Briant, D.J.,Zarrine-Afsar, A.,Sicheri, F.,Kay, L.E.,Pawson, T.
Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain
Proc.Natl.Acad.Sci.Usa, 104:14336-14341, 2007

PubMed Abstract: The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studies of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.

PubMed: 17726107
DOI: 10.1073/pnas.0703012104

実験手法

X-RAY DIFFRACTION (2.7 Å)