1U3O

Solution structure of rat Kalirin N-terminal SH3 domain

Summary for 1U3O

• Entry DOI: 10.2210/pdb1u3o/pdb
• NMR Information: BMRB: 6300
• Descriptor: Huntingtin-associated protein-interacting protein (1 entity in total)
• Functional Keywords: sh3, cis-proline, signaling protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm: P97924
• Total number of polymer chains: 1
• Total formula weight: 8578.58

Authors

Schiller, M.R.,Chakrabarti, K.,King, G.F.,Schiller, N.I.,Eipper, B.A.,Maciejewski, M.W. (deposition date: 2004-07-22, release date: 2005-07-26, Last modification date: 2024-05-22)

Primary citation

Schiller, M.R.,Chakrabarti, K.,King, G.F.,Schiller, N.I.,Eipper, B.A.,Maciejewski, M.W.
Regulation of RhoGEF Activity by Intramolecular and Intermolecular SH3 Domain Interactions.
J.Biol.Chem., 281:18774-18786, 2006

PubMed Abstract: RhoGEFs are central controllers of small G-proteins in cells and are regulated by several mechanisms. There are at least 22 human RhoGEFs that contain SH3 domains, raising the possibility that, like several other enzymes, SH3 domains control the enzymatic activity of guanine nucleotide exchange factor (GEF) domains through intra- and/or intermolecular interactions. The structure of the N-terminal SH3 domain of Kalirin was solved using NMR spectroscopy, and it folds much like other SH3 domains. However, NMR chemical shift mapping experiments showed that this Kalirin SH3 domain is unique, containing novel cooperative binding site(s) for intramolecular PXXP ligands. Intramolecular Kalirin SH3 domain/ligand interactions, as well as binding of the Kalirin SH3 domain to the adaptor protein Crk, inhibit the GEF activity of Kalirin. This study establishes a novel molecular mechanism whereby intramolecular and intermolecular Kalirin SH3 domain/ligand interactions modulate GEF activity, a regulatory mechanism that is likely used by other RhoGEF family members.

PubMed: 16644733
DOI: 10.1074/jbc.M512482200

Experimental method

SOLUTION NMR