6CLZ

MT1-MMP HPX domain with Blade 4 Loop Bound to Nanodiscs

  • Classification: LIPID BINDING PROTEIN
  • Organism(s): Homo sapiens
  • Expression System: Escherichia coli
  • Mutation(s): No 

  • Deposited: 2018-03-02 Released: 2018-12-12 
  • Deposition Author(s): Marcink, T.C., Van Doren, S.R.
  • Funding Organization(s): National Institutes of Health/National Cancer Institute (NIH/NCI), National Institutes of Health/National Center for Research Resources (NIH/NCRR)

Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 15 
  • 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

MT1-MMP Binds Membranes by Opposite Tips of Its beta Propeller to Position It for Pericellular Proteolysis.

Marcink, T.C.Simoncic, J.A.An, B.Knapinska, A.M.Fulcher, Y.G.Akkaladevi, N.Fields, G.B.Van Doren, S.R.

(2019) Structure 27: 281-292.e6

  • DOI: https://doi.org/10.1016/j.str.2018.10.008
  • Primary Citation of Related Structures:  
    6CLZ, 6CM1

  • PubMed Abstract: 

    Critical to migration of tumor cells and endothelial cells is the proteolytic attack of membrane type 1 matrix metalloproteinase (MT1-MMP) upon collagen, growth factors, and receptors at cell surfaces. Lipid bilayer interactions of the substrate-binding hemopexin-like (HPX) domain of MT1-MMP were investigated by paramagnetic nuclear magnetic resonance relaxation enhancements (PREs), fluorescence, and mutagenesis. The HPX domain binds bilayers by blades II and IV on opposite sides of its β propeller fold. The EPGYPK sequence protruding from both blades inserts among phospholipid head groups in PRE-restrained molecular dynamics simulations. Bilayer binding to either blade II or IV exposes the CD44 binding site in blade I. Bilayer association with blade IV allows the collagen triple helix to bind without obstruction. Indeed, vesicles enhance proteolysis of collagen triple-helical substrates by the ectodomain of MT1-MMP. Hypothesized side-by-side MT1-MMP homodimerization would allow binding of bilayers, collagen, CD44, and head-to-tail oligomerization.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Matrix metalloproteinase-14196Homo sapiensMutation(s): 0 
Gene Names: MMP14
EC: 3.4.24.80
UniProt & NIH Common Fund Data Resources
Find proteins for P50281 (Homo sapiens)
Explore P50281 
Go to UniProtKB:  P50281
PHAROS:  P50281
GTEx:  ENSG00000157227 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50281
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Apolipoprotein A-I
B, C
211Homo sapiensMutation(s): 0 
Gene Names: APOA1
UniProt & NIH Common Fund Data Resources
Find proteins for P02647 (Homo sapiens)
Explore P02647 
Go to UniProtKB:  P02647
PHAROS:  P02647
GTEx:  ENSG00000118137 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02647
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]
AC [auth B]
AD [auth B]
AE [auth B]
AF [auth C]
AA [auth A],
AC [auth B],
AD [auth B],
AE [auth B],
AF [auth C],
AG [auth C],
AH [auth C],
BA [auth A],
BB [auth B],
BC [auth B],
BD [auth B],
BE [auth B],
BF [auth C],
BG [auth C],
BH [auth C],
CA [auth A],
CB [auth B],
CC [auth B],
CD [auth B],
CE [auth B],
CF [auth C],
CG [auth C],
CH [auth C],
D [auth A],
DA [auth A],
DB [auth B],
DC [auth B],
DD [auth B],
DE [auth B],
DF [auth C],
DG [auth C],
DH [auth C],
E [auth A],
EA [auth A],
EB [auth B],
EC [auth B],
ED [auth B],
EE [auth B],
EF [auth C],
EG [auth C],
EH [auth C],
F [auth A],
FA [auth A],
FB [auth B],
FC [auth B],
FD [auth B],
FE [auth B],
FF [auth C],
FG [auth C],
FH [auth C],
G [auth A],
GA [auth A],
GB [auth B],
GC [auth B],
GD [auth B],
GE [auth B],
GF [auth C],
GG [auth C],
GH [auth C],
H [auth A],
HA [auth A],
HB [auth B],
HC [auth B],
HD [auth B],
HE [auth B],
HF [auth C],
HG [auth C],
HH [auth C],
I [auth A],
IA [auth A],
IB [auth B],
IC [auth B],
ID [auth B],
IE [auth B],
IF [auth C],
IG [auth C],
IH [auth C],
J [auth A],
JA [auth A],
JB [auth B],
JC [auth B],
JD [auth B],
JE [auth B],
JF [auth C],
JG [auth C],
JH [auth C],
K [auth A],
KA [auth A],
KB [auth B],
KC [auth B],
KD [auth B],
KE [auth B],
KF [auth C],
KG [auth C],
KH [auth C],
L [auth A],
LA [auth A],
LB [auth B],
LC [auth B],
LD [auth B],
LE [auth B],
LF [auth C],
LG [auth C],
LH [auth C],
M [auth A],
MA [auth A],
MB [auth B],
MC [auth B],
MD [auth B],
ME [auth B],
MF [auth C],
MG [auth C],
MH [auth C],
N [auth A],
NA [auth A],
NB [auth B],
NC [auth B],
ND [auth B],
NE [auth B],
NF [auth C],
NG [auth C],
NH [auth C],
O [auth A],
OA [auth A],
OB [auth B],
OC [auth B],
OD [auth B],
OE [auth B],
OF [auth C],
OG [auth C],
OH [auth C],
P [auth A],
PA [auth A],
PB [auth B],
PC [auth B],
PD [auth B],
PE [auth B],
PF [auth C],
PG [auth C],
Q [auth A],
QA [auth A],
QB [auth B],
QC [auth B],
QD [auth B],
QE [auth B],
QF [auth C],
QG [auth C],
R [auth A],
RA [auth A],
RB [auth B],
RC [auth B],
RD [auth B],
RE [auth B],
RF [auth C],
RG [auth C],
S [auth A],
SA [auth A],
SB [auth B],
SC [auth B],
SD [auth B],
SE [auth B],
SF [auth C],
SG [auth C],
T [auth A],
TA [auth A],
TB [auth B],
TC [auth B],
TD [auth B],
TE [auth B],
TF [auth C],
TG [auth C],
U [auth A],
UA [auth A],
UB [auth B],
UC [auth B],
UD [auth B],
UE [auth B],
UF [auth C],
UG [auth C],
V [auth A],
VA [auth A],
VB [auth B],
VC [auth B],
VD [auth B],
VE [auth B],
VF [auth C],
VG [auth C],
W [auth A],
WA [auth A],
WB [auth B],
WC [auth B],
WD [auth B],
WE [auth B],
WF [auth C],
WG [auth C],
X [auth A],
XA [auth A],
XB [auth B],
XC [auth B],
XD [auth B],
XE [auth C],
XF [auth C],
XG [auth C],
Y [auth A],
YA [auth A],
YB [auth B],
YC [auth B],
YD [auth B],
YE [auth C],
YF [auth C],
YG [auth C],
Z [auth A],
ZB [auth B],
ZC [auth B],
ZD [auth B],
ZE [auth C],
ZF [auth C],
ZG [auth C]
1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
C36 H73 N O8 P
CITHEXJVPOWHKC-UUWRZZSWSA-O
CL
Query on CL

Download Ideal Coordinates CCD File 
AB [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
ZA [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesR01 CA098799
National Institutes of Health/National Center for Research Resources (NIH/NCRR)United StatesS10 RR022341

Revision History  (Full details and data files)

  • Version 1.0: 2018-12-12
    Type: Initial release
  • Version 1.1: 2019-02-20
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-04
    Changes: Author supporting evidence, Data collection