A Conserved Interdomain Interaction Is a Determinant of Folding Cooperativity in the GST Fold

Biochemistry ◽  
2011 ◽  
Vol 50 (32) ◽  
pp. 7067-7075 ◽  
Author(s):  
Nishal Parbhoo ◽  
Stoyan H. Stoychev ◽  
Sylvia Fanucchi ◽  
Ikechukwu Achilonu ◽  
Roslin J. Adamson ◽  
...  
Keyword(s):  
Interdomain Interaction

scholarly journals Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition

2018 ◽  
Vol 115 (51) ◽  
pp. E11933-E11942 ◽  
Author(s):  
Jinqi Ren ◽  
Shuang Wang ◽  
Han Chen ◽  
Wenjuan Wang ◽  
Lin Huo ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Underlying Mechanism ◽  
Motor Domain ◽  
Dimer Formation ◽  
Interaction Interface ◽  
Adp Release ◽  
Interdomain Interaction ◽  
Neck Domain ◽  
Neck Coil

In kinesin-3, the coiled-coil 1 (CC1) can sequester the preceding neck coil (NC) for autoinhibition, but the underlying mechanism is poorly understood. Here, we determined the structures of the uninhibited motor domain (MD)-NC dimer and inhibited MD-NC-CC1 monomer of kinesin-3 KIF13B. In the MD-NC-CC1 monomer, CC1 is broken into two short helices that unexpectedly interact with both the NC and the MD. Compared with the MD-NC dimer, the CC1-mediated integration of NC and MD not only blocks the NC dimer formation, but also prevents the neck linker (NL) undocking and the ADP release from the MD. Mutations of the essential residues in the interdomain interaction interface in the MD-NC-CC1 monomer restored the MD activity. Thus, CC1 fastens the neck domain and MD and inhibits both NC and NL. This CC1-mediated lockdown of the entire neck domain may represent a paradigm for kinesin autoinhibition that could be applicable to other kinesin-3 motors.

scholarly journals CNGA3 achromatopsia-associated mutation potentiates the phosphoinositide sensitivity of cone photoreceptor CNG channels by altering intersubunit interactions

2013 ◽  
Vol 305 (2) ◽  
pp. C147-C159 ◽  
Author(s):  
Gucan Dai ◽  
Michael D. Varnum
Keyword(s):  
Leucine Zipper ◽  
Sensory Transduction ◽  
Cone Photoreceptor ◽  
Electrophysiological Recordings ◽  
Retinal Photoreceptors ◽  
Functional Consequences ◽  
Interdomain Interaction ◽  
Channel Assembly ◽  
Intersubunit Interactions ◽  
The Impact

Cyclic nucleotide-gated (CNG) channels are critical for sensory transduction in retinal photoreceptors and olfactory receptor cells; their activity is modulated by phosphoinositides (PIPn) such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). An achromatopsia-associated mutation in cone photoreceptor CNGA3, L633P, is located in a carboxyl (COOH)-terminal leucine zipper domain shown previously to be important for channel assembly and PIPn regulation. We determined the functional consequences of this mutation using electrophysiological recordings of patches excised from cells expressing wild-type and mutant CNG channel subunits. CNGA3-L633P subunits formed functional channels with or without CNGB3, producing an increase in apparent cGMP affinity. Surprisingly, L633P dramatically potentiated PIPn inhibition of apparent cGMP affinity for these channels. The impact of L633P on PIPn sensitivity depended on an intact amino (NH2) terminal PIPn regulation module. These observations led us to hypothesize that L633P enhances PIPn inhibition by altering the coupling between NH2- and COOH-terminal regions of CNGA3. A recombinant COOH-terminal fragment partially restored normal PIPn sensitivity to channels with COOH-terminal truncation, but L633P prevented this effect. Furthermore, coimmunoprecipitation of channel fragments, and thermodynamic linkage analysis, also provided evidence for NH2-COOH interactions. Finally, tandem dimers of CNGA3 subunits that specify the arrangement of subunits containing L633P and other mutations indicated that the putative interdomain interaction occurs between channel subunits (intersubunit) rather than exclusively within the same subunit (intrasubunit). Collectively, these studies support a model in which intersubunit interactions control the sensitivity of cone CNG channels to regulation by phosphoinositides. Aberrant channel regulation may contribute to disease progression in patients with the L633P mutation.

Optical Spectroscopic Characterization of Single Tryptophan Mutants of Chicken Skeletal Troponin C:  Evidence for Interdomain Interaction†

Biochemistry ◽  
1999 ◽  
Vol 38 (37) ◽  
pp. 11973-11983 ◽  
Author(s):  
Martin C. Moncrieffe ◽  
Sergei Yu. Venyaminov ◽  
Todd E. Miller ◽  
Georgiana Guzman ◽  
James D. Potter ◽  
...  
Keyword(s):  
Spectroscopic Characterization ◽  
Troponin C ◽  
Interdomain Interaction

scholarly journals Malignant hyperthermia mutation sites in the Leu2442–Pro2477 (DP4) region of RyR1 (ryanodine receptor 1) are clustered in a structurally and functionally definable area

2006 ◽  
Vol 401 (1) ◽  
pp. 333-339 ◽  
Author(s):  
Mark L. Bannister ◽  
Tomoyo Hamada ◽  
Takashi Murayama ◽  
Peta J. Harvey ◽  
Marco G. Casarotto ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Structural Studies ◽  
Amino Acid Residues ◽  
Domain Interaction ◽  
Closed State ◽  
Interdomain Interaction ◽  
Ryanodine Receptor 1 ◽  
Domain Peptide ◽  
Interdomain Interactions

To explain the mechanism of pathogenesis of channel disorder in MH (malignant hyperthermia), we have proposed a model in which tight interactions between the N-terminal and central domains of RyR1 (ryanodine receptor 1) stabilize the closed state of the channel, but mutation in these domains weakens the interdomain interaction and destabilizes the channel. DP4 (domain peptide 4), a peptide corresponding to residues Leu2442–Pro2477 of the central domain, also weakens the domain interaction and produces MH-like channel destabilization, whereas an MH mutation (R2458C) in DP4 abolishes these effects. Thus DP4 and its mutants serve as excellent tools for structure–function studies. Other MH mutations have been reported in the literature involving three other amino acid residues in the DP4 region (Arg2452, Ile2453 and Arg2454). In the present paper we investigated the activity of several mutants of DP4 at these three residues. The ability to activate ryanodine binding or to effect Ca2+ release was severely diminished for each of the MH mutants. Other substitutions were less effective. Structural studies, using NMR analysis, revealed that the peptide has two α-helical regions. It is apparent that the MH mutations are clustered at the C-terminal end of the first helix. The data in the present paper indicates that mutation of residues in this region disrupts the interdomain interactions that stabilize the closed state of the channel.

Sign in / Sign up

Export Citation Format

Share Document