Structural bases for recognition of Anp32/LANP proteins.
The leucine-rich repeat acidic nuclear protein (Anp32a/LANP) belongs to a family of evolutionarily-conserved phosphoproteins involved in a complex network of protein-protein interactions. In an effort to understand the cellular role, we have investigated the mode of interaction of Anp32a with its partners. As a prerequisite, we solved the structure in solution of the evolutionarily conserved N-terminal leucine-rich repeat (LRR) domain and modeled its interactions with other proteins, taking PP2A as a paradigmatic example. The interaction between the Anp32a LRR domain and the AXH domain of ataxin-1 was probed experimentally. The two isolated and unmodified domains bind with very weak (millimolar) affinity, thus suggesting the necessity either for an additional partner (e.g. other regions of either or both proteins or a third molecule) or for a post-translational modification. Finally, we identified by two-hybrid screening a new partner of the LRR domain, i.e. the microtubule plus-end tracking protein Clip 170/Restin, known to regulate the dynamic properties of microtubules and to be associated with severe human pathologies.
de Chiara
Cesira
C
National Institute for Medical Research, The Ridgeway, London, UK.
Menon
Rajesh P
RP
Pastore
Annalisa
A
D000595:Amino Acid Sequence; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D020798:Two-Hybrid System Techniques
C087425:ANP32A protein, human; C000593749:ATXN1 protein, human; C530107:Anp32a protein, mouse; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C076744:cytoplasmic linker protein 170; D054648:Protein Phosphatase 2