title: Structural insights into the intrinsic self-assembly of Par-3 N-terminal domain.
abstract: Par-3, the central organizer of the Par-3/Par-6/atypical protein kinase C complex, is a multimodular scaffold protein that is essential for cell polarity establishment and maintenance. The N-terminal domain (NTD) of Par-3 is capable of self-association to form filament-like structures, although the underlying mechanism is poorly understood. Here, we determined the crystal structure of Par-3 NTD and solved the filament structure by cryoelectron microscopy. We found that an intrinsic "front-to-back" interaction mode is important for Par-3 NTD self-association and that both the lateral and longitudinal packing within the filament are mediated by electrostatic interactions. Disruptions of the lateral or longitudinal packing significantly impaired Par-3 NTD self-association and thereby impacted the Par-3-mediated epithelial polarization. We finally demonstrated that a Par-3 NTD-like domain from histidine ammonia-lyase also harbors a similar self-association capacity. This work unequivocally provides the structural basis for Par-3 NTD self-association and characterizes one type of protein domain that can self-assemble via electrostatic interactions.
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
authors: Yan
authors: Y
authors: Zhang
authors: Wenjuan
authors: W
authors: Wang
authors: Jia
authors: J
authors: Chen
authors: Kai
authors: K
authors: Zhang
authors: Feng
authors: F
authors: Gao
authors: Bingquan
authors: B
authors: Gao
authors: Shuai
authors: S
authors: Zhang
authors: Mingdong
authors: M
authors: Dong
authors: Flemming
authors: F
authors: Besenbacher
authors: Weimin
authors: W
authors: Gong
authors: Mingjie
authors: M
authors: Zhang
authors: Fei
authors: F
authors: Sun
authors: Wei
authors: W
authors: Feng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000737:chemistry*; D020285:Cryoelectron Microscopy; D008565:Membrane Proteins / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human