Interesting structural and dynamical behaviors exhibited by the AF-6 PDZ domain upon Bcr peptide binding.
PDZ (postsynaptic density-95, disks large, zonula occludens-1) domains are small, protein-protein interaction modules that have multiple binding surfaces for the docking of diverse molecules. These domains can propagate signals from ligand-binding site to distal regions of the structure through allosteric communication. Recent works have revealed that picosecond to nanosecond time scale dynamics play a potential role in propagating long-range signals within a protein. Comparison of AF-6 PDZ domain structures in free and complex forms shows a conformation rearrangement of distal surface 2, which is far from the peptide binding groove. The relaxation dispersion experiments detected that the free AF-6 PDZ domain was sampling multiple conformations; millisecond dynamics mapped a network for allostery signal transmission throughout the AF-6 PDZ domain in the weak saturation state, and intramolecular motions were observed in distal surface 1 when the protein was saturated. These results provide evidence that the allosteric process in the AF-6 PDZ domain is not two-state; instead, the millisecond dynamic network provides a mechanism for the transmission of allosteric signals throughout a protein. Interestingly, the two distal surfaces of the AF-6 PDZ domain respond differently to peptide binding; distal surface 1 changes in millisecond dynamics, whereas distal surface 2 undergoes structural rearrangement. The significance of the different response patterns in the signaling pathway and its relevance to the function of the AF-6 PDZ domain should be studied further.
Niu
Xiaogang
X
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, and School of Life Sciences, Hefei, Anhui 230026, People's Republic of China.
Chen
Quan
Q
Zhang
Jiahai
J
Shen
Weiqun
W
Shi
Yunyu
Y
Wu
Jihui
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D054731:PDZ Domains; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D051562:Proto-Oncogene Proteins c-bcr / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
C095516:AFDN protein, human; D010446:Peptide Fragments; D051562:Proto-Oncogene Proteins c-bcr; D009218:Myosins; D016547:Kinesins