Kinetic intermediates in the formation of the cytochrome c molten globule.
Abstract
The relationship between molten globules and transient intermediates in protein folding has been explored by equilibrium and kinetic analysis of the compact acid-denatured A-state of cytochrome c. The chloride-induced formation of the A-state is a complex reaction with structural intermediates resembling those found under native refolding conditions, including a rapidly formed compact state and a subsequent intermediate with interacting N- and C-terminal helices. Together with mutational evidence for specific helix-helix packing interactions, this shows that the A-state is a stable analogue of a late folding intermediate. The L94A mutation blocks all folding steps after the initial collapse and its equilibrium state resembles early kinetic intermediates. Study holds ProTherm entries: 7416, 7417, 7418, 7419, 7420, 7421, 7422, 7423, 14391 Extra Details:
Submission Details
ID: n6Y3Ln2K3
Submitter: Connie Wang
Submission Date: April 24, 2018, 8:34 p.m.
Version: 1
Publication Details
Colón W;Roder H,Nat. Struct. Biol. (1996) Kinetic intermediates in the formation of the cytochrome c molten globule. PMID:8946855Additional Information
Study Summary
| Number of data points | 18 |
| Proteins | Cytochrome c ; Cytochrome c |
| Unique complexes | 3 |
| Assays/Quantities/Protocols | Experimental Assay: ddG ; Experimental Assay: Tm ; Experimental Assay: dHvH ; Experimental Assay: Cm ; Experimental Assay: dG_H2O ; Experimental Assay: Cm ; Experimental Assay: dG_H2O ; Derived Quantity: dTm |
| Libraries | Mutations for sequence GDVEKGKKIFVQKCAQCHTVEKGGKHKTGPNLHGLFGRKTGQAPGFTYTDANKNKGITWKEETLMEYLENPKKYIPGTKMIFAGIKKKTEREDLIAYLKKATNE |
Structure view and single mutant data analysis
Study data
| 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 |
|---|---|---|---|
| 1LC1 | 2003-06-03 | Solution Structure Of Reduced Horse Heart Cytochrome c in 30% Acetonitrile Solution, NMR Minimized Average Structure | |
| 1GIW | 1998-12-09 | SOLUTION STRUCTURE OF REDUCED HORSE HEART CYTOCHROME C, NMR, MINIMIZED AVERAGE STRUCTURE | |
| 1FI9 | 2000-08-23 | SOLUTION STRUCTURE OF THE IMIDAZOLE COMPLEX OF CYTOCHROME C | |
| 5ZKV | 2019-05-22 | Solution structure of molten globule state of L94G mutant of horse cytochrome-c | |
| 1AKK | 1997-09-17 | SOLUTION STRUCTURE OF OXIDIZED HORSE HEART CYTOCHROME C, NMR, MINIMIZED AVERAGE STRUCTURE | |
| 1LC2 | 2003-06-03 | Solution Structure Of Reduced Horse Heart Cytochrome c in 30% Acetonitrile Solution, NMR 30 Structures | |
| 1I5T | 2001-03-21 | SOLUTION STRUCTURE OF CYANOFERRICYTOCHROME C | |
| 2FRC | 1997-07-29 | CYTOCHROME C (REDUCED) FROM EQUUS CABALLUS, NMR, MINIMIZED AVERAGE STRUCTURE | |
| 2N3B | 2015-10-28 | Structure of oxidized horse heart cytochrome c encapsulated in reverse micelles | |
| 2GIW | 1998-12-09 | SOLUTION STRUCTURE OF REDUCED HORSE HEART CYTOCHROME C, NMR, 40 STRUCTURES | |
| 1OCD | 1997-06-16 | CYTOCHROME C (OXIDIZED) FROM EQUUS CABALLUS, NMR, MINIMIZED AVERAGE STRUCTURE | |
| 1FI7 | 2000-08-23 | Solution structure of the imidazole complex of cytochrome C | |
| 1M60 | 2002-08-07 | Solution Structure of Zinc-substituted cytochrome c | |
| 5C0Z | 2016-09-21 | 1.12 | The structure of oxidized rat cytochrome c at 1.13 angstroms resolution |
| 5DF5 | 2016-09-14 | 1.3 | The structure of oxidized rat cytochrome c (T28E) at 1.30 angstroms resolution. |
| 5C9M | 2016-09-21 | 1.36 | The structure of oxidized rat cytochrome c (T28A) at 1.362 angstroms resolution. |
| 2B4Z | 2005-10-11 | 1.5 | Crystal structure of cytochrome C from bovine heart at 1.5 A resolution. |
| 6N1O | 2019-10-23 | 1.55 | Oxidized rat cytochrome c mutant (S47E) |
| 6FF5 | 2018-03-21 | 1.74 | X-ray structure of bovine heart cytochrome c at high ionic strength |
| 3O1Y | 2012-01-25 | 1.75 | Electron transfer complexes: Experimental mapping of the redox-dependent cytochrome c electrostatic surface |
| 3WUI | 2014-07-16 | 1.8 | Dimeric horse cytochrome c formed by refolding from molten globule state |
| 3WC8 | 2013-12-11 | 1.8 | Dimeric horse cytochrome c obtained by refolding with desalting method |
| 1WEJ | 1998-12-09 | 1.8 | IGG1 FAB FRAGMENT (OF E8 ANTIBODY) COMPLEXED WITH HORSE CYTOCHROME C AT 1.8 A RESOLUTION |
| 3O20 | 2012-01-25 | 1.9 | Electron transfer complexes:experimental mapping of the Redox-dependent Cytochrome C electrostatic surface |
| 1HRC | 1994-11-01 | 1.9 | HIGH-RESOLUTION THREE-DIMENSIONAL STRUCTURE OF HORSE HEART CYTOCHROME C |
| 2YBB | 2011-10-19 | 19.0 | Fitted model for bovine mitochondrial supercomplex I1III2IV1 by single particle cryo-EM (EMD-1876) |
| 5IY5 | 2017-01-11 | 2.0 | Electron transfer complex of cytochrome c and cytochrome c oxidase at 2.0 angstrom resolution |
| 1CRC | 1996-03-08 | 2.08 | CYTOCHROME C AT LOW IONIC STRENGTH |
| 3NBT | 2010-07-14 | 2.1 | Crystal structure of trimeric cytochrome c from horse heart |
| 4NFG | 2014-09-24 | 2.11 | K13R mutant of horse cytochrome c and yeast cytochrome c peroxidase complex |
| 4RSZ | 2015-01-14 | 2.19 | The X-ray structure of the Primary Adduct formed in the Reaction between Cisplatin and Cytochrome c |
| 3NBS | 2010-07-14 | 2.2 | Crystal structure of dimeric cytochrome c from horse heart |
| 1KTD | 2002-05-01 | 2.4 | CRYSTAL STRUCTURE OF CLASS II MHC MOLECULE IEK BOUND TO PIGEON CYTOCHROME C PEPTIDE |
| 1U75 | 2004-09-28 | 2.55 | Electron Transfer Complex between Horse Heart Cytochrome c and Zinc-Porphyrin Substituted Cytochrome c Peroxidase |
| 2PCB | 1993-07-15 | 2.8 | CRYSTAL STRUCTURE OF A COMPLEX BETWEEN ELECTRON TRANSFER PARTNERS, CYTOCHROME C PEROXIDASE AND CYTOCHROME C |
| 3JBT | 2015-11-18 | 3.8 | Atomic structure of the Apaf-1 apoptosome |
| 5JUY | 2016-10-19 | 4.1 | Active human apoptosome with procaspase-9 |
| 5WVE | 2017-02-08 | 4.4 | Apaf-1-Caspase-9 holoenzyme |
| 3J2T | 2013-04-10 | 9.5 | An improved model of the human apoptosome |
Relevant UniProtKB Entries
| Percent Identity | Matching Chains | Protein | Accession | Entry Name |
|---|---|---|---|---|
| 100.0 | Cytochrome c | P00004 | CYC_HORSE | |
| 99.0 | Cytochrome c | P68097 | CYC_EQUAS | |
| 99.0 | Cytochrome c | P68096 | CYC_EQUBU | |
| 97.1 | Cytochrome c | P62894 | CYC_BOVIN | |
| 97.1 | Cytochrome c | P62895 | CYC_PIG | |
| 97.1 | Cytochrome c | P62896 | CYC_SHEEP | |
| 94.3 | Cytochrome c | P00007 | CYC_HIPAM | |
| 95.2 | Cytochrome c | P68099 | CYC_CAMDR | |
| 95.2 | Cytochrome c | P68100 | CYC_ESCRO | |
| 95.2 | Cytochrome c | P68098 | CYC_LAMGU | |
| 94.3 | Cytochrome c | P62897 | CYC_MOUSE | |
| 94.3 | Cytochrome c | P00008 | CYC_RABIT | |
| 94.3 | Cytochrome c | P62898 | CYC_RAT | |
| 94.3 | Cytochrome c | P00011 | CYC_CANLF | |
| 93.3 | Cytochrome c | P00014 | CYC_MACGI | |
| 93.3 | Cytochrome c | P00013 | CYC_MINSC | |
| 93.3 | Cytochrome c | Q52V09 | CYC_CEPBA | |
| 93.3 | Cytochrome c | P00012 | CYC_MIRLE | |
| 90.5 | Cytochrome c | Q52V10 | CYC_SAISC | |
| 92.3 | Cytochrome c | P81280 | CYC_ALLMI | |
| 92.2 | Cytochrome c | P00020 | CYC_ANAPL | |
| 91.3 | Cytochrome c | P00021 | CYC_COLLI | |
| 90.3 | Cytochrome c | B4USV4 | CYC_OTOGA |