4IHB

X-RAY STRUCTURE OF THE canonical C2A DOMAIN FROM HUMAN DYSFERLIN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.204 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Alternate Splicing of Dysferlin C2A Confers Ca(2+)-Dependent and Ca(2+)-Independent Binding for Membrane Repair.

Fuson, K.Rice, A.Mahling, R.Snow, A.Nayak, K.Shanbhogue, P.Meyer, A.G.Redpath, G.M.Hinderliter, A.Cooper, S.T.Sutton, R.B.

(2014) Structure 22: 104-115

  • DOI: https://doi.org/10.1016/j.str.2013.10.001
  • Primary Citation of Related Structures:  
    4IHB, 4IQH

  • PubMed Abstract: 

    Dysferlin plays a critical role in the Ca²⁺-dependent repair of microlesions that occur in the muscle sarcolemma. Of the seven C2 domains in dysferlin, only C2A is reported to bind both Ca²⁺ and phospholipid, thus acting as a key sensor in membrane repair. Dysferlin C2A exists as two isoforms, the "canonical" C2A and C2A variant 1 (C2Av1). Interestingly, these isoforms have markedly different responses to Ca²⁺ and phospholipid. Structural and thermodynamic analyses are consistent with the canonical C2A domain as a Ca²⁺-dependent, phospholipid-binding domain, whereas C2Av1 would likely be Ca²⁺-independent under physiological conditions. Additionally, both isoforms display remarkably low free energies of stability, indicative of a highly flexible structure. The inverted ligand preference and flexibility for both C2A isoforms suggest the capability for both constitutive and Ca²⁺-regulated effector interactions, an activity that would be essential in its role as a mediator of membrane repair.


  • Organizational Affiliation

    Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dysferlin
A, B, C, D, E
A, B, C, D, E, F
133Homo sapiensMutation(s): 0 
Gene Names: DYSFFER1L1
UniProt & NIH Common Fund Data Resources
Find proteins for O75923 (Homo sapiens)
Explore O75923 
Go to UniProtKB:  O75923
PHAROS:  O75923
GTEx:  ENSG00000135636 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75923
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FMT
Query on FMT

Download Ideal Coordinates CCD File 
AA [auth D]
BA [auth D]
CA [auth D]
DA [auth D]
EA [auth D]
AA [auth D],
BA [auth D],
CA [auth D],
DA [auth D],
EA [auth D],
FA [auth D],
G [auth A],
GA [auth D],
H [auth A],
HA [auth D],
I [auth A],
IA [auth D],
J [auth A],
JA [auth D],
K [auth A],
KA [auth D],
L [auth A],
LA [auth E],
M [auth A],
MA [auth E],
N [auth A],
NA [auth E],
O [auth B],
OA [auth E],
P [auth B],
PA [auth E],
Q [auth B],
QA [auth E],
R [auth B],
S [auth B],
SA [auth F],
T [auth B],
TA [auth F],
U [auth B],
V [auth C],
W [auth C],
X [auth C],
Y [auth C],
Z [auth D]
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
RA [auth E]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.204 
  • Space Group: I 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 102.413α = 90
b = 70.67β = 113.39
c = 118.31γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-12-18
    Type: Initial release
  • Version 1.1: 2014-01-29
    Changes: Database references
  • Version 1.2: 2018-04-25
    Changes: Data collection
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description