2MLS

Membrane Bilayer complex with Matrix Metalloproteinase-12 at its Beta-face


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 14 
  • Conformers Submitted: 14 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12.

Koppisetti, R.K.Fulcher, Y.G.Jurkevich, A.Prior, S.H.Xu, J.Lenoir, M.Overduin, M.Van Doren, S.R.

(2014) Nat Commun 5: 5552-5552

  • DOI: https://doi.org/10.1038/ncomms6552
  • Primary Citation of Related Structures:  
    2MLR, 2MLS

  • PubMed Abstract: 

    Matrix metalloproteinases (MMPs) regulate tissue remodelling, inflammation and disease progression. Some soluble MMPs are inexplicably active near cell surfaces. Here we demonstrate the binding of MMP-12 directly to bilayers and cellular membranes using paramagnetic NMR and fluorescence. Opposing sides of the catalytic domain engage spin-labelled membrane mimics. Loops project from the β-sheet interface to contact the phospholipid bilayer with basic and hydrophobic residues. The distal membrane interface comprises loops on the other side of the catalytic cleft. Both interfaces mediate MMP-12 association with vesicles and cell membranes. MMP-12 binds plasma membranes and is internalized to hydrophobic perinuclear features, the nuclear membrane and inside the nucleus within minutes. While binding of TIMP-2 to MMP-12 hinders membrane interactions beside the active site, TIMP-2-inhibited MMP-12 binds vesicles and cells, suggesting compensatory rotation of its membrane approaches. MMP-12 association with diverse cell membranes may target its activities to modulate innate immune responses and inflammation.


  • Organizational Affiliation

    Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, Missouri 65211, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Macrophage metalloelastase164Homo sapiensMutation(s): 1 
Gene Names: MMP12HME
EC: 3.4.24.65
UniProt & NIH Common Fund Data Resources
Find proteins for P39900 (Homo sapiens)
Explore P39900 
Go to UniProtKB:  P39900
PHAROS:  P39900
GTEx:  ENSG00000262406 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP39900
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PX4
Query on PX4

Download Ideal Coordinates CCD File 
AA [auth A]
AB [auth A]
AC [auth A]
AD [auth A]
AE [auth A]
AA [auth A],
AB [auth A],
AC [auth A],
AD [auth A],
AE [auth A],
BA [auth A],
BB [auth A],
BC [auth A],
BD [auth A],
CA [auth A],
CB [auth A],
CC [auth A],
CD [auth A],
DA [auth A],
DB [auth A],
DC [auth A],
DD [auth A],
EA [auth A],
EB [auth A],
EC [auth A],
ED [auth A],
FA [auth A],
FB [auth A],
FC [auth A],
FD [auth A],
G [auth A],
GA [auth A],
GB [auth A],
GC [auth A],
GD [auth A],
H [auth A],
HA [auth A],
HB [auth A],
HC [auth A],
HD [auth A],
I [auth A],
IA [auth A],
IB [auth A],
IC [auth A],
ID [auth A],
J [auth A],
JA [auth A],
JB [auth A],
JC [auth A],
JD [auth A],
K [auth A],
KA [auth A],
KB [auth A],
KC [auth A],
KD [auth A],
L [auth A],
LA [auth A],
LB [auth A],
LC [auth A],
LD [auth A],
M [auth A],
MA [auth A],
MB [auth A],
MC [auth A],
MD [auth A],
N [auth A],
NA [auth A],
NB [auth A],
NC [auth A],
ND [auth A],
O [auth A],
OA [auth A],
OB [auth A],
OC [auth A],
OD [auth A],
P [auth A],
PA [auth A],
PB [auth A],
PC [auth A],
PD [auth A],
Q [auth A],
QA [auth A],
QB [auth A],
QC [auth A],
QD [auth A],
R [auth A],
RA [auth A],
RB [auth A],
RC [auth A],
RD [auth A],
S [auth A],
SA [auth A],
SB [auth A],
SC [auth A],
SD [auth A],
T [auth A],
TA [auth A],
TB [auth A],
TC [auth A],
TD [auth A],
U [auth A],
UA [auth A],
UB [auth A],
UC [auth A],
UD [auth A],
V [auth A],
VA [auth A],
VB [auth A],
VC [auth A],
VD [auth A],
W [auth A],
WA [auth A],
WB [auth A],
WC [auth A],
WD [auth A],
X [auth A],
XA [auth A],
XB [auth A],
XC [auth A],
XD [auth A],
Y [auth A],
YA [auth A],
YB [auth A],
YC [auth A],
YD [auth A],
Z [auth A],
ZA [auth A],
ZB [auth A],
ZC [auth A],
ZD [auth A]
1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
C36 H73 N O8 P
CITHEXJVPOWHKC-UUWRZZSWSA-O
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

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

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 14 
  • Conformers Submitted: 14 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-12-03
    Type: Initial release
  • Version 1.1: 2014-12-10
    Changes: Database references
  • Version 1.2: 2024-05-01
    Changes: Data collection, Database references, Derived calculations