2frw
From Proteopedia
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'''Solution structure of the second SH3 domain of human adaptor protein NCK2'''<br /> | '''Solution structure of the second SH3 domain of human adaptor protein NCK2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human Nck2 (hNck2) is a 380-residue adapter protein consisting of three | + | Human Nck2 (hNck2) is a 380-residue adapter protein consisting of three SH3 domains and one SH2 domain. Nck2 plays a pivotal role in connecting and integrating signaling networks constituted by transmembrane receptors such as ephrinB and effectors critical for cytoskeletonal dynamics and remodeling. In this study, we aimed to determine the NMR structures and dynamic properties of the hNck2 SH3 domains and to define their ligand binding preferences with nine proline-rich peptides derived from Wire, CAP-1, CAP-2, Prk, Wrch1, Wrch2, and Nogo. The results indicate (1) the first hNck2 SH3 domain is totally insoluble. On the other hand, although the second and third hNck2 SH3 domains adopt a conserved SH3 fold, they exhibit distinctive dynamic properties. Interestingly, the third SH3 domain has a far-UV CD spectrum typical of a largely unstructured protein but exhibits {1H}-15N steady-state NOE values larger than 0.7 for most residues. (2) The HSQC titrations revealed that the two SH3 domains have differential ligand preferences. The second SH3 domain seems to prefer a consensus sequence of APx#PxR, while the third SH3 domain prefers PxAPxR. (3) Several high-affinity bindings were identified for hNck2 SH3 domains by isothermal titration calorimetry. In particular, the binding of SH3-3 with the Nogo-A peptide was discovered and shown to exhibit a Kd of 5.7 microM. Interestingly, of the three SH3-binding motifs carried by Wrch1, only the middle one was capable of binding SH3-2. Our results provide valuable clues for further functional investigations into the Nck2-mediated signaling networks. |
==About this Structure== | ==About this Structure== | ||
| - | 2FRW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2FRW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FRW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: sh3]] | [[Category: sh3]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:24:36 2008'' |
Revision as of 15:24, 21 February 2008
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Solution structure of the second SH3 domain of human adaptor protein NCK2
Overview
Human Nck2 (hNck2) is a 380-residue adapter protein consisting of three SH3 domains and one SH2 domain. Nck2 plays a pivotal role in connecting and integrating signaling networks constituted by transmembrane receptors such as ephrinB and effectors critical for cytoskeletonal dynamics and remodeling. In this study, we aimed to determine the NMR structures and dynamic properties of the hNck2 SH3 domains and to define their ligand binding preferences with nine proline-rich peptides derived from Wire, CAP-1, CAP-2, Prk, Wrch1, Wrch2, and Nogo. The results indicate (1) the first hNck2 SH3 domain is totally insoluble. On the other hand, although the second and third hNck2 SH3 domains adopt a conserved SH3 fold, they exhibit distinctive dynamic properties. Interestingly, the third SH3 domain has a far-UV CD spectrum typical of a largely unstructured protein but exhibits {1H}-15N steady-state NOE values larger than 0.7 for most residues. (2) The HSQC titrations revealed that the two SH3 domains have differential ligand preferences. The second SH3 domain seems to prefer a consensus sequence of APx#PxR, while the third SH3 domain prefers PxAPxR. (3) Several high-affinity bindings were identified for hNck2 SH3 domains by isothermal titration calorimetry. In particular, the binding of SH3-3 with the Nogo-A peptide was discovered and shown to exhibit a Kd of 5.7 microM. Interestingly, of the three SH3-binding motifs carried by Wrch1, only the middle one was capable of binding SH3-2. Our results provide valuable clues for further functional investigations into the Nck2-mediated signaling networks.
About this Structure
2FRW 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 human Nck2 SH3 domains and proline-rich proteins., Liu J, Li M, Ran X, Fan JS, Song J, Biochemistry. 2006 Jun 13;45(23):7171-84. PMID:16752908
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