Altered dynamics in Lck SH3 upon binding to the LBD1 domain of Herpesvirus saimiri Tip.
The Tip protein from Herpesvirus saimiri interacts with the SH3 domain from the Src-family kinase Lck via a proline-containing sequence termed LBD1. Src-family kinase SH3 domains related to Lck have been shown to be dynamic in solution and partially unfold under physiological conditions. The rate of such partial unfolding is reduced by viral protein binding. To determine if the Lck SH3 domain displayed similar behavior, the domain was investigated with hydrogen exchange and mass spectrometry. Lck SH3 was found to be highly dynamic in solution. While other SH3 domains require as much as 10,000 sec to become totally deuterated, Lck SH3 became almost completely labeled within 200 sec. A partial unfolding event involving 8-10 residues was observed with a half-life of approximately 10 sec. Tip LBD1 binding did not cause gross structural changes in Lck SH3 but globally stabilized the domain and reduced the rate of partial unfolding by a factor of five. The region of partial unfolding in Lck SH3 was found to be similar to that identified for other SH3 domains that partially unfold. Although the sequence conservation between Lck SH3 and other closely related SH3 domains is high, the dynamics do not appear to be conserved.
Weis
David D
DD
Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131, USA.
Kjellen
Peter
P
Sefton
Bartholomew M
BM
Engen
John R
JR
D001665:Binding Sites; D041961:Deuterium Exchange Measurement; D006567:Herpesvirus 2, Saimiriine / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism; D018909:src Homology Domains
D010750:Phosphoproteins; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)