7DMD
Solution structure of human Aha1 N-terminal domain
Summary for 7DMD
| Entry DOI | 10.2210/pdb7dmd/pdb |
| Descriptor | Activator of 90 kDa heat shock protein ATPase homolog 1 (1 entity in total) |
| Functional Keywords | n-terminal domain of human activator of hsp90 atpase homolog 1, structural protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15135.94 |
| Authors | |
| Primary citation | Hu, H.,Wang, Q.,Du, J.,Liu, Z.,Ding, Y.,Xue, H.,Zhou, C.,Feng, L.,Zhang, N. Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity. Molecules, 26:-, 2021 Cited by PubMed Abstract: Aha1 is the only co-chaperone known to strongly stimulate the ATPase activity of Hsp90. Meanwhile, besides the well-studied co-chaperone function, human Aha1 has also been demonstrated to exhibit chaperoning activity against stress-denatured proteins. To provide structural insights for a better understanding of Aha1's co-chaperone and chaperone-like activities, nuclear magnetic resonance (NMR) techniques were used to reveal the unique structure and internal dynamics features of full-length human Aha1. We then found that, in solution, both the two domains of Aha1 presented distinctive thermal stabilities and dynamics behaviors defined by their primary sequences and three-dimensional structures. The low thermal stability (melting temperature of Aha1: 54.45 °C) and the internal dynamics featured with slow motions on the µs-ms time scale were detected for Aha1's N-terminal domain (Aha1N). The aforementioned experimental results suggest that Aha1N is in an energy-unfavorable state, which would therefore thermostatically favor the interaction of Aha1N with its partner proteins such as Hsp90's middle domain. Differently from Aha1N, Aha1C (Aha1's C-terminal domain) exhibited enhanced thermal stability (melting temperature of Aha1: 72.41 °C) and the internal dynamics featured with intermediate motions on the ps-ns time scale. Aha1C's thermal and structural stabilities make it competent for the stabilization of the exposed hydrophobic groove of dimerized Hsp90's N-terminal domain. Of note, according to the NMR data and the thermal shift results, although the very N-terminal region (M1-W27) and the C-terminal relaxin-like factor (RLF) motif showed no tight contacts with the remaining parts of human Aha1, they were identified to play important roles in the recognition of intrinsically disordered pathological α-synuclein. PubMed: 33808352DOI: 10.3390/molecules26071943 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
