Jacky Huynh | Khtn - Academia.edu (original) (raw)
Address: Dung, Thanh Hoa, Vietnam
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University of Texas M. D. Anderson Cancer Center
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Papers by Jacky Huynh
Biochemistry, 2009
ASF/SF2, a member of the serine-arginine (SR) protein family, has two RRM domains (RRM1 and RRM2)... more ASF/SF2, a member of the serine-arginine (SR) protein family, has two RRM domains (RRM1 and RRM2) and a C-terminus domain rich in RS dipeptides. The SR protein kinase 1 (SRPK1) phosphorylates approximately 12 of these serines using a semi-processive mechanism. The x-ray structure of the ASF/SF2:SRPK1 complex revealed several features of the complex that raised intriguing questions of how the substrate is phosphorylated by the kinase: The part of the RS domain destined to be phosphorylated at later stages of the reaction docks to a kinase groove distal to the active site while the neighboring RRM2 binds near the active site (1). In this study we investigated the interplay between the RS domain and RRM2 for stable association and phosphorylation of ASF/SF2. Despite several contacts in the enzyme-substrate complex, free RRM2 does not bind efficiently to SRPK1 unless the docking groove is occupied by the RS domain. This domain cross-talk enhances the processive phosphorylation of the RS domain. The RRM:SRPK1 contact residues control the folding of a critical beta strand in RRM2. Unfolding of this structural element may force the N-terminal serines of the RS domain into the active site for sequential phosphorylation. Thus, ASF/SF2 represents a new class of substrates that use unique primary sequence to induce allosteric binding, processive phosphorylation, and product release.
Biochemistry, 2009
ASF/SF2, a member of the serine-arginine (SR) protein family, has two RRM domains (RRM1 and RRM2)... more ASF/SF2, a member of the serine-arginine (SR) protein family, has two RRM domains (RRM1 and RRM2) and a C-terminus domain rich in RS dipeptides. The SR protein kinase 1 (SRPK1) phosphorylates approximately 12 of these serines using a semi-processive mechanism. The x-ray structure of the ASF/SF2:SRPK1 complex revealed several features of the complex that raised intriguing questions of how the substrate is phosphorylated by the kinase: The part of the RS domain destined to be phosphorylated at later stages of the reaction docks to a kinase groove distal to the active site while the neighboring RRM2 binds near the active site (1). In this study we investigated the interplay between the RS domain and RRM2 for stable association and phosphorylation of ASF/SF2. Despite several contacts in the enzyme-substrate complex, free RRM2 does not bind efficiently to SRPK1 unless the docking groove is occupied by the RS domain. This domain cross-talk enhances the processive phosphorylation of the RS domain. The RRM:SRPK1 contact residues control the folding of a critical beta strand in RRM2. Unfolding of this structural element may force the N-terminal serines of the RS domain into the active site for sequential phosphorylation. Thus, ASF/SF2 represents a new class of substrates that use unique primary sequence to induce allosteric binding, processive phosphorylation, and product release.