7OOJ

Structure of D-Thr53 Ubiquitin

Summary for 7OOJ

• Entry DOI: 10.2210/pdb7ooj/pdb
• Descriptor: Ubiquitin, CADMIUM ION (3 entities in total)
• Functional Keywords: ubiquitin, synthetic d-thr53 mutant, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 18141.05

Authors

Becker, S. (deposition date: 2021-05-27, release date: 2022-05-18, Last modification date: 2024-11-20)

Primary citation

Chakrabarti, K.S.,Olsson, S.,Pratihar, S.,Giller, K.,Overkamp, K.,Lee, K.O.,Gapsys, V.,Ryu, K.S.,de Groot, B.L.,Noe, F.,Becker, S.,Lee, D.,Weikl, T.R.,Griesinger, C.
A litmus test for classifying recognition mechanisms of transiently binding proteins.
Nat Commun, 13:3792-3792, 2022

PubMed Abstract: Partner recognition in protein binding is critical for all biological functions, and yet, delineating its mechanism is challenging, especially when recognition happens within microseconds. We present a theoretical and experimental framework based on straight-forward nuclear magnetic resonance relaxation dispersion measurements to investigate protein binding mechanisms on sub-millisecond timescales, which are beyond the reach of standard rapid-mixing experiments. This framework predicts that conformational selection prevails on ubiquitin's paradigmatic interaction with an SH3 (Src-homology 3) domain. By contrast, the SH3 domain recognizes ubiquitin in a two-state binding process. Subsequent molecular dynamics simulations and Markov state modeling reveal that the ubiquitin conformation selected for binding exhibits a characteristically extended C-terminus. Our framework is robust and expandable for implementation in other binding scenarios with the potential to show that conformational selection might be the design principle of the hubs in protein interaction networks.

PubMed: 35778416
DOI: 10.1038/s41467-022-31374-5

Experimental method

X-RAY DIFFRACTION (2.6 Å)