2L3Q

Structure of the prolyl trans isomer of the Crk Protein

Summary for 2L3Q

• Entry DOI: 10.2210/pdb2l3q/pdb
• Related: 2L3P 2L3S
• Descriptor: Trans isomer of Crk protein (1 entity in total)
• Functional Keywords: adapter protein, structural protein
• Biological source: Gallus gallus (bantam,chickens)
• Cellular location: Cytoplasm (By similarity): Q04929
• Total number of polymer chains: 1
• Total formula weight: 8731.95

Authors

Kalodimos, C.,Sarkar, P.,Saleh, T.,Tzeng, S.,Birge, R. (deposition date: 2010-09-21, release date: 2010-12-08, Last modification date: 2024-05-01)

Primary citation

Sarkar, P.,Saleh, T.,Tzeng, S.R.,Birge, R.B.,Kalodimos, C.G.
Structural basis for regulation of the Crk signaling protein by a proline switch.
Nat.Chem.Biol., 7:51-57, 2011

PubMed Abstract: Proline switches, controlled by cis-trans isomerization, have emerged as a particularly effective regulatory mechanism in a wide range of biological processes. Here we report the structures of both the cis and trans conformers of a proline switch in the Crk signaling protein. Proline isomerization toggles Crk between two conformations: an autoinhibitory conformation, stabilized by the intramolecular association of two tandem SH3 domains in the cis form, and an uninhibited, activated conformation promoted by the trans form. In addition to acting as a structural switch, the heterogeneous proline recruits cyclophilin A, which accelerates the interconversion rate between the isomers, thereby regulating the kinetics of Crk activation. The data provide atomic insight into the mechanisms that underpin the functionality of this binary switch and elucidate its remarkable efficiency. The results also reveal new SH3 binding surfaces, highlighting the binding versatility and expanding the noncanonical ligand repertoire of this important signaling domain.

PubMed: 21131971
DOI: 10.1038/nchembio.494

Experimental method

SOLUTION NMR