1z3k
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(New page: 200px<br /> <applet load="1z3k" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z3k" /> '''Structural Insight into the Binding Diversi...)
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Revision as of 18:22, 12 November 2007
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Structural Insight into the Binding Diversity between the Tyr-Phosphorylated Human EphrinBs and Nck2 SH2 Domain
Overview
The binding interaction between the Nck2 SH2 domain and the phosphorylated, ephrinB initiates a critical pathway for the reverse signaling network, mediated by Eph receptor-ephrinB. Previously, the NMR structure and Tyr, phosphorylations of the human ephrinB cytoplasmic domain have been, studied. To obtain a complete story, it would be of significant interest, to determine the structure of the Nck2 SH2 domain that shows a low, sequence identity to other SH2 domains with known structures. Here, we, report the determination of the solution structure of the human Nck2 SH2, domain and investigate its interactions with three phosphorylated ephrinB, fragments by NMR spectroscopy. The results indicate that: 1) although the, human Nck2 SH2 domain adopts a core tertiary fold common to all SH2, domains, it owns some unique properties such as a shorter C-terminal helix, and unusual electrostatic potential surface. However, the most striking, finding is that the C-terminal tail of the human Nck2 SH2 domain adopts a, short antiparallel beta-sheet that, to the best of our knowledge, has, never been identified in other SH2 domains. The truncation study suggests, that one function of the C-terminal tail is to control the, folding/solubility of the SH2 domain. 2) In addition to, [Tyr(P)304]ephrinB2(301-322) and [Tyr(P)316]ephrinB2(301-322), here we, identified [Tyr(P)330]ephrinB2(324-333) also capable of binding to the SH2, domain. The detailed NMR study indicated that the binding mechanisms for, the three ephrinB fragments might be different. The binding with, [Tyr(P)304]-ephrinB2(301-322) and [Tyr(P)316]ephrinB2(301-322) might be, mostly involved in the residues over the N-half of the SH2 domain and, provoked a significant increase in the backbone and side chain dynamics of, the SH2 domain on the microsecond-millisecond time scale. In contrast, binding with [Tyr(P)330]ephrinB2(324-333) might have most residues over, both halves engaged but induced less profound conformational dynamics on, the mus-ms time scale.
About this Structure
1Z3K is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain., Ran X, Song J, J Biol Chem. 2005 May 13;280(19):19205-12. Epub 2005 Mar 11. PMID:15764601
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