Partial unfolding of diverse SH3 domains on a wide timescale.


Abstract

SH3 domains are small, modular domains that are found in many proteins, especially signal transduction proteins such as tyrosine kinases. While much is known about the sequences and tertiary structures of SH3 domains, far less is known about their solution dynamics. A slow, partial unfolding event that occurs under physiological conditions was previously identified in the Hck SH3 domain using hydrogen exchange (HX) mass spectrometry (MS). To determine if this unfolding was unique to Hck SH3, HX MS was used to analyze 11 other SH3 domains: seven SH3 domains from Src-family kinases and five SH3 domains from various proteins. A wide variety of unfolding rates were found, with unfolding half-lives ranging from 1s to 1h. The Lyn and alpha-spectrin SH3 domains exhibited slow, partial unfolding in beta strands D and E and part of the RT-loop. Hck SH3 also underwent partial unfolding in the same region, implying that a unique feature in this area of the domains is responsible for the partial unfolding. Partial unfolding was, however, not a function of sequence conservation. Although the Fyn and Yes SH3 domains are very similar to Hck SH3 in sequence, they exhibited no evidence of partial unfolding. Overall, the results suggest that while the tertiary structure of SH3 domains is highly conserved, the dynamics of SH3 domains are variable. Study holds ProTherm entries: 22139, 22140, 22141 Extra Details: SH3 domain hydrogen exchange; mass spectrometry; protein dynamics; Src-family kinases

Submission Details

ID: gdYd9VaR

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:53 p.m.

Version: 1

Publication Details
Wales TE;Engen JR,J. Mol. Biol. (2006) Partial unfolding of diverse SH3 domains on a wide timescale. PMID:16487539
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
3THK 2011-08-19T00:00:00+0000 1.7 Structure of SH3 chimera with a type II ligand linked to the chain C-terminal
1W1F 2004-06-17T00:00:00+0000 0 SH3 DOMAIN OF HUMAN LYN TYROSINE KINASE
1WA7 2004-10-25T00:00:00+0000 0 SH3 DOMAIN OF HUMAN LYN TYROSINE KINASE IN COMPLEX WITH A HERPESVIRAL LIGAND
2ZV7 2008-11-04T00:00:00+0000 2.5 Lyn Tyrosine Kinase Domain, apo form
2ZV8 2008-11-04T00:00:00+0000 2.7 Lyn Tyrosine Kinase Domain-AMP-PNP complex
2ZV9 2008-11-04T00:00:00+0000 2.76 Lyn Tyrosine Kinase Domain-PP2 complex
2ZVA 2008-11-04T00:00:00+0000 2.6 Lyn Tyrosine Kinase Domain-Dasatinib complex
3A4O 2009-07-11T00:00:00+0000 3.0 Lyn kinase domain
4TZI 2014-07-10T00:00:00+0000 2.1 Structure of unliganded Lyn SH2 domain
5XY1 2017-07-05T00:00:00+0000 2.7 Crystal structure of Lyn kinase domain in complex with N-(1H-indazol-6-yl)-8-(piperidin-4-yloxy)-6-propylquinazolin-2-amine

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Spectrin alpha chain, non-erythrocytic 1 P07751 SPTN1_CHICK
100.0 Spectrin alpha chain, non-erythrocytic 1 Q13813 SPTN1_HUMAN
100.0 Spectrin alpha chain, non-erythrocytic 1 P16086 SPTN1_RAT
100.0 Spectrin alpha chain, non-erythrocytic 1 P16546 SPTN1_MOUSE
100.0 Tyrosine-protein kinase HCK P08631 HCK_HUMAN
98.2 Tyrosine-protein kinase HCK Q95M30 HCK_MACFA
93.3 Tyrosine-protein kinase HCK P50545 HCK_RAT
93.0 Tyrosine-protein kinase HCK P08103 HCK_MOUSE
100.0 Tyrosine-protein kinase Lyn P07948 LYN_HUMAN
94.3 Tyrosine-protein kinase Lyn Q07014 LYN_RAT
94.3 Tyrosine-protein kinase Lyn P25911 LYN_MOUSE