THE MINOR LAB Home of the Electrosome

Structures

EMC:Cavcomplex

EMC:Cav1.2(ΔC):Cavβ3 complex
PDB: 8EOI
EMDB:EMD-2878, EMD-28579, EMD-40559, EMD-40560

EMC chaperone-CaV structure reveals an ion channel assembly intermediate. Chen Z, Mondal, A., Aberemane-Ali, F., Jang, S., Niranjan, S., Montaño, J.L., Zaro, B.W., Minor, D.L., Jr. Nature  619 410-419 (2023)

Cav1.2 structures

Cav1.2(ΔC):Cavβ3Cavα2δ-1 complexed with L-Leu
PDB: 8EOG
EMDB:EMD-28375, EMD-28561, EMD-28564, EMD-40561

Cav1.2(ΔC):Cavβ3Cavα2δ-1 complexed with gabapentin
PDB: 8FD7
EMDB:EMD-29004, EMD-29007, EMD-29015

EMC chaperone-CaV structure reveals an ion channel assembly intermediate. Chen Z, Mondal, A., Aberemane-Ali, F., Jang, S., Niranjan, S., Montaño, J.L., Zaro, B.W., Minor, D.L., Jr. Nature  619 410-419 (2023)

Structural basis for CaVɑ 2δ:gabapentin binding. Chen Z, Mondal A, and Minor, D.L., Jr. Nature Struct. & Mol. Biol. 30 735-739 (2023)

 

Nanobody: Cavβ complexes

Cavβ1b:nb.E8
PDB: 8DAM

Cavβ2a:nb.F3
PDB: 8EOE

Selective posttranslational inhibition of CaVβ1-associated voltage-dependent calcium channels with a functionalized nanobody. Morgenstern, T., Nirwan, N., Hernandez-Ochoa, E., Bibollet, H., Choudhury, P., Laloudakis, J., Ben-Johny, M., Bannister, R., Schneider, M., Minor, D.L., Jr., and Colecraft, H.M. Nature Communications 13:7556 (2022)

 

Saxiphilin variants and complexes

American bullfrog (R. castesbeiana) saxphilin (RcSxph) mutants

RcSxph-Y558A 
PDB: 8D6P

RcSxph-Y558A:STX 
PDB: 8D6T

RcSxph-Y558I 
PDB: 8D6Q

RcSxph-Y558I:STX 
PDB: 8D6T

RcSxph:F-STX (Flourescein-STX) 
PDB: 8D6P

High Himalaya Frog (N. parkeri), saxiphilin (NpSxph) 
PDB: 8D6G

NpSxph:STX 
PDB: 8D6M

NpSxph:F-STX 
PDB: 8D6O

Definition of a saxitoxin (STX) binding code enables discovery and characterization of the Anuran saxiphilin family. Chen, Z., Zakrzewska, S., Hajare, H., Alvarez-Bullya, A., Abderemane-Ali, F., Bogan, M., Ramirez, D., O’Connell, L.A., Du Bois, J., and Minor, D.L., Jr. Proceedings of the National Academy of Sciences, USA 119:e2210114119 (2022)

 

Non-canonical BacNaV pore domain structures

NavAb1p (DM-detergent) ‘Inside-out’
PDB: 7PGG

NavAb1p (bicelles) ‘Inside-out’
PDB: 7PGI

CavSp1p (bicelles) ‘PeripheralSF’
PDB: 7PGF

NavAe1/Sp1CTDp (DDM-detergent) ‘Inside-out’
PDB: 7PGH

Fab complexes

NavAe1/Sp1CTDp:SAT09 complex
PDB: 7PGB

NavAe1/Sp1CTDp:ANT05 complex 
PDB: 7PG8

Quaternary structure independent folding of voltage-gated ion channel pore domain subunits. Arrigoni, C., Lolicato, M., Shaya, D., Rohaim, A., Findeisen, F., Fong, L.-K., Colleran, C.M., Dominik, P., Kim, S.S., Schuermann, J., DeGrado, W.F., Grabe, M., Kossiakoff, A.A., and Minor, D.L., Jr. Nature Structural and Molecular Biology 29: 537-548 (2022)

 

K2P2.1 (TREK-1) in varied potassium concentrations

K2P2.1 (TREK-1), 0 mM [K+]
PDB: 6W7B

K2P2.1 (TREK-1), 1 mM [K+]
PDB: 6W7C

K2P2.1(TREK-1), 10 mM [K+]
PDB: 6W7D

K2P2.1 (TREK-1), 30 mM [K+]
PDB: 6W7E

K2P2.1 (TREK-1), 50 mM [K+]
PDB: 6W82

K2P2.1 (TREK-1), 100 mM [K+]
PDB: 6W83

K2P2.1 (TREK-1), 200 mM [K+]
PDB: 6W84

K2P2.1 (TREK-1):ML335 complex, 0 mM [K+]
PDB: 6W8F

K2P2.1 (TREK-1):ML335 complex, 1 mM [K+]
PDB:6W8C

K2P2.1 (TREK-1):ML335 complex, 10 mM [K+]
PDB: 6W8A

K2P2.1(TREK-1):ML335 complex, 30 mM [K+]
PDB: 6W88

K2P2.1 (TREK-1):ML335 complex, 50 mM [K+]
PDB: 6W87

K2P2.1 (TREK-1):ML335 complex, 100 mM [K+]
PDB: 6W86

K2P2.1 (TREK-1):ML335 complex, 200 mM [K+]
PDB: 6W85

K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.  Lolicato, M., Natale, A.M., Abderemane-Ali, F., Crottes, D., Capponi, S., Duman, R. Wagner, A., Rosenberg, J.M., Grabe, M., Minor, D.L. Jr. Science Advances 6 eabc9174 (2020)

K2P2.1 (TREK-1):Polynuclear ruthenium amine complexes

K2P2.1 (TREK-1) I110D
PDB: 6V36

K2P2.1 (TREK-1) I110D:Ruthenium red
PDB: 6V3I

K2P2.1 (TREK-1) I110D:Ruthenium red:ML335
PDB: 6V37

K2P2.1 (TREK-1) I110D:Ru360
PDB: 6V3C

Polynuclear Ruthenium Amines Inhibit K2P Channels via a "Finger in the Dam" Mechanism. Pope, L., Lolicato, M., Minor, D.L. Jr. Cell Chemical Biology 27: 511-524 (2020)

Saxiphilin and Saxiphilin:STX complexes

Saxiphilin

Apo-Saxiphilin
PDB ID: 6O0D

Saxiphilin: STX complexes

Saxiphilin:STX complex (soaked)
PDB ID: 6O0E

Saxiphilin:STX complex (co-crystal)
PDB ID: 6O0F

Structure of the saxiphilin:saxitoxin (STX)complex reveals a convergent molecular recognition strategy for paralytic toxins. Yen, T.-J., Lolicato, M., Thomas-Tran, R., Du Bois, J., and Minor, D.L. Jr., Science Advances 5 eaax2650 (2019) PMID: 31223657 PMCID: PMC6584486 View Press

Saxiphilin

CaM:Kv7.4 AB domain complexes & CaM:Kv7.5 AB domain complex

CaM:Kv7.4 AB domain complexes:

Apo/CaM:Kv7.4 AB domain complex
PDB ID: 6B8L

Ca2+/CaM:Kv7.4 AB domain complex, 1 mM CaCl2 soak
PDB ID: 6B8M

Ca2+/CaM:Kv7.4 AB domain complex, 10  µM CaCl2 soak
PDB ID: 6B8N

Mg2+/CaM:Kv7.4 AB domain complex
PDB ID: 6B8P

CaM:7.5 AB domain complex:

Mg2+/CaM:Kv7.5 AB domain complex
PDB ID: 6B8Q

A Calmodulin C-Lobe Ca2+-Dependent Switch Governs Kv7 Channel Function. Chang, A., Abderemane-Ali, F., Hura, G.L., Rossen, N.D., Gate, R.E., Minor, D.L., Jr., Neuron 97 836-852 (2018) View Video Abstract PMID:29429937 PMCID: PMC5823783

6B8L

TMEM16A calcium-activated chloride channel

Cryo-EM structure of the TMEM16A calcium-activated chloride channel in nanodisc
PDB ID: 6BGI

Cryo-EM structure of the TMEM16A calcium-activated chloride channel in LMNG
PDB: 6BGJ

Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Dang S., Feng S., Tien J., Peters C.J., Bulkley D., Lolicato M., Zhao J., Zuberbühler K., Ye W., Qi L., Chen T., Craik C.S., Nung Jan Y., Minor D.L. Jr, Cheng Y., Yeh Jan L., Nature 552 426-429 (2017) PMID: 29236684 PMCID: PMC5750132 

6BGI

Coagulation Factor XI:antibody complex

FXIa/ DEF Fab complex coordinates
PDB: 6AOD

Structural basis for activity and specificity of an anticoagulant anti-FXIa monoclonal antibody and a reversal agent. Ely, L., Lolicato, M. David, T., Lowe, K., Kim, Y.C., Samuel, D., Bessette, P., Garcia, J.L., Mikita, T., Minor, D.L. Jr., Coughlin, S.R., Structure 26187-198 (2018) 

6AOD

Mouse K2P2.1 (TREK-1)

K2P2.1 (TREK-1)
PDB ID: 5VK5

Mouse K2P2.1 (TREK-1): Activator Complexes

ML335 complex
PDB ID: 5VKN

ML402 complex
PDB ID: 5VKP

K2P2.1(TREK-1):activator complexes reveal a cryptic selectivity filter binding site. Lolicato, M., Arrigoni, C., Mori, T., Sekioka, Y., Bryant, C., Clark, K.A., Minor, D.L., Jr., Nature 547 364-368 (2017) PMID: 28693035 PMCID: PMC5778891

5VKP

CaVβ: Stapled peptide complexes

AID-CAP PDB ID: 5V2P
AID-CEN PDB ID: 5V2Q

Stapled voltage-gated calcium channel (CaV) α-Interaction Domain (AID) peptides act as selective protein-protein interaction inhibitors of CaV Function. Findeisen, F., Campiglio, M., Jo, H., Abderemane-Ali, F., Rumpf, C.H., Pope, L., Rossen, N.D., Flucher, B.E., DeGrado, W.F., and Minor D.L., Jr., ACS Chemical Neuroscience 8 1313-1326 (2017) PMID: 28278376 PMCID: PMC5481814

5V2P

Human K2P4.1 (TRAAK)

G124I
PDB ID: 4RUE

W262S
PDB ID: 4RUF

Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K2P channels.
Lolicato, M., Riegelhaupt, P.M., Arrigoni, C., Clark, K.A., Minor, D.L., Jr., Neuron 84 1198-1212 (2014) PMID: 25500157 PMCID: PMC4270892

4RUF

NaVAe1p (Alkalilimnicola ehrlichii)

PDB IDs: 4LTO, 4LTP, 4LTQ, and 4LTR

Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels.
Shaya, D., Findeisen, F., Abderemane-Ali, F., Arrigoni, C., Wong, S., Reddy Nurva, S., Loussouarn, G., and Minor, D.L., Jr., Journal of Molecular Biology 426 476-483 (2014) PMID: 24120938 PMCID: PMC3947372
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PDB IDs: NaVAe1p 2.95Å: 5HK7, 5IWO, 5IWN, 3G neck mutant: 5HJ8, 5HK6, 7G neck mutant: 5HKD

Unfolding of a temperature-sensitive domain controls voltage-gated channel activation.
Arrigoni, C., Rohaim, A., Shaya, D., Findeisen, F., Stein, R.A. Nurva, S.R., Mishra, S., Mchaourab, H.S., and Minor, D.L., Jr., Cell 164 922‑936 (2016) 

Crystal structure of Ciona intestinalis voltage sensor-containing phosphatase

PDB IDs: 3V0D, 3V0E, 3V0F, 3V0G, 3V0H, 3V0I, 3V0J

A glutamate switch controls voltage-sensitive phosphatase function.
Liu L., Kohout, S.C., Xu, Q., Müller, S., Kimberlin, C.R., Isacoff, E.Y. Minor, D.L., Jr., Nature Structural and Molecular Biology 19 633-641 (2012) PMID: 22562138 PMCID: PMC3529583

Ca2+CaM:Kv7.4 (KCNQ4) B-helix complex

PDB ID: 4GOW

Structure of a Ca2+/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M-current modulation.
Xu, Q., Chang, A., Tolia, A., and Minor, D.L., Jr., Journal of Molecular Biology 425 378-394 (2013) PMID: 23178170 PMCID:PMC3540129

Ca2+/CaM-CaV1.2 PreIQ-IQ domain complex

PDB ID: 3OXQ

Multiple C-terminal tail Ca2+/CaMs regulate CaV1.2 function but do not mediate channel dimerization.
Kim, E., Rumpf, C., Van Petegem, F., Arant, R.J., Findeisen, F., Cooley, E., Isacoff, E., Minor, Jr., D.L., The EMBO Journal 29, 3924-3938 (2010)

CaBP1 and CaBP1 K130A

CaBP1
PDB ID: 3OX5

CaBP1 K130A
PDB ID: 3OX6

Structural Basis for the Differential Effects of CaBP1 and Calmodulin on CaV1.2 Calcium-Dependent Inactivation.
Findeisen, F., Minor, Jr., D.L., Structure 18, 1617–1631 (2010)

A trimeric form of the KV7.1 A domain Tail

TRPM7 Assembly Domain

PDB ID: 3E7K

Fujiwara, Y., Minor, Jr., D.L. X-ray Crystal Structure of a TRPM Assembly Domain Reveals an Antiparallel Four-stranded Coiled-coil.
J. Mol. Biol. 383, 854-870 (2008).

3E7K

CaV 2.1 IQ domain-Ca2+/Calmodulin Complex

PDB ID: 3DVM

Kim, E.Y., Rumpf, C.H., Fujiwara, Y., Cooley, E.S., Van Petegem, F., and Minor, Jr., D.L. Structures of CaV2 Ca2+/CaM-IQ Domain Complexes Reveal Binding Modes that Underlie Calcium-Dependent Inactivation and Facilitation.
Structure 16, 1455-1467 (2008).

3DVM

CaV 2.2 IQ domain-Ca2+/Calmodulin Complex

PDB IDs: 3DVE, 3DVJ

Kim, E.Y., Rumpf, C.H., Fujiwara, Y., Cooley, E.S., Van Petegem, F., and Minor, Jr., D.L. Structures of CaV2 Ca2+/CaM-IQ Domain Complexes Reveal Binding Modes that Underlie Calcium-Dependent Inactivation and Facilitation. Structure 16, 1455-1467 (2008).

3DVE

CaV 2.3 IQ domain-Ca2+/Calmodulin Complex

PDB ID: 3DVK

Kim, E.Y., Rumpf, C.H., Fujiwara, Y., Cooley, E.S., Van Petegem, F., and Minor, Jr., D.L. Structures of CaV2 Ca2+/CaM-IQ Domain Complexes Reveal Binding Modes that Underlie Calcium-Dependent Inactivation and Facilitation. Structure 16, 1455-1467 (2008).

3DVK

Kv7.4 (KCNQ4) assembly specificity domain

2OVC Kv7.4 (KCNQ4) Assembly Specificity Domain
PDB ID: 2OVC

Structural insight into KCNQ (Kv7) channel assembly and channelopathy.
Howard, R.J., Clark, K.A., Holton, J.M., and Minor, Jr., D.L., Neuron 53 663-675 (2007)

2OVC

KChIP1/Kv4.3 T1 domain complex

2I2R KChIP1/Kv4.3 T1 Domain Complex
PDB ID: 212R

Three-dimensional structure of the KChIP/Kv4.3 T1 domain complex reveals a cross-shaped octamer. Pioletti, M., Findeisen, F., Hura, G.L., and Minor, Jr., D.L., Nature Structural & Molecular Biology 13 987 995 (2006)

212R

Voltage-gated Potassium Channel T1 assembly domain

1QDW Kv1.2 T1 domain 33-119
PDB ID: 1QDW

1QDV Kv1.2 T1 domain 33-131
PDB ID: 1QDV

1DSX KV1.2 T1 domain33-131 T46V mutant
PDB ID: 1DSX

The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel. Minor, Jr., D.L., Lin, Y.F, Mobley, B.C., Avelar, A., Jan, Y.N., Jan, L.Y. and Berger, J.M., Cell 102 657-670 (2000)

1QDW

Voltage-gated Calcium Channel β-subunit

1T0H CaVβ2a
PDB ID: 1TOH

1T0J CaVβ2a - CaV1.2 AID complex
PDB ID: 1TOJ

Structure of a complex between a voltage gated calcium channel beta-subunit and an alpha-subunit domain. Van Petegem, F., Clark, K.A., Chatelain, F.C., and Minor, Jr., D.L., Nature 429 671-675 (2004)

1TOH

CaV1.2 IQ domain-Ca2+/Calmodulin Complex

2BE6 CaV1.2 IQ domain-Ca2+/CaM complex
PDB ID: 2BE6

Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex. Van Petegem, F, Chatelain, F.C., Minor, Jr., D.L., Nature Structural & Molecular Biology 12 1108-1115 (2005)

2BE6