Dynamin

Vesicle formation GTPase family

Protein family

Dynamin family

Structure of the nucleotide-free myosin II motor domain from Dictyostelium discoideum fused to the GTPase domain of dynamin I from Rattus norvegicus

Identifiers
Symbol| Dynamin_N
Pfam| PF00350
Pfam clan| CL0023
InterPro| IPR001401
PROSITE| PDOC00362
| Available protein structures:

Pfam  | structures / ECOD
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary

Protein family

Dynamin central region

Structure of the nucleotide-free myosin II motor domain from Dictyostelium discoideum fused to the GTPase domain of dynamin I from Rattus norvegicus

Identifiers
Symbol| Dynamin_M
Pfam| PF01031
InterPro| IPR000375
| Available protein structures:

Pfam  | structures / ECOD
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary

Dynamin is a GTPase protein responsible for endocytosis in the eukaryotic cell. Dynamin is part of the "dynamin superfamily", which includes classical dynamins, dynamin-like proteins, Mx proteins, OPA1, mitofusins, and GBPs. Members of the dynamin family are principally involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface (particularly caveolae internalization) as well as at the Golgi apparatus.[1][2][3] Dynamin family members also play a role in many processes including division of organelles,[4] cytokinesis and microbial pathogen resistance.

## Structure

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Dynamin assembled into helical polymers as visualized by negative stain electron microscopy.[5]

Dynamin itself is a 96 kDa enzyme, and was first isolated when researchers were attempting to isolate new microtubule-based motors from the bovine brain. Dynamin has been extensively studied in the context of clathrin-coated vesicle budding from the cell membrane.[3][6] Beginning from the N-terminus, Dynamin consists of a GTPase domain connected to a helical stalk domain via a flexible neck region containing a Bundle Signalling Element and GTPase Effector Domain. At the opposite end of the stalk domain is a loop that links to a membrane-binding Pleckstrin homology domain. The protein strand then loops back towards the GTPase domain and terminates with a Proline Rich Domain that binds to the Src Homology domains of many proteins.

## Function

[edit]

During clathrin-mediated endocytosis, the cell membrane invaginates to form a budding vesicle. Dynamin binds to and assembles around the neck of the endocytic vesicle, forming a helical polymer arranged such that the GTPase domains dimerize in an asymmetric manner across helical rungs.[7][8] The polymer constricts the underlying membrane upon GTP binding and hydrolysis via conformational changes emanating from the flexible neck region that alters the overall helical symmetry.[8] Constriction around the vesicle neck leads to the formation of a hemi-fission membrane state that ultimately results in membrane scission.[2][6][9] Constriction may be in part the result of the twisting activity of dynamin, which makes dynamin the only molecular motor known to have a twisting activity.[10]

## Types

[edit]

In mammals, three different dynamin genes have been identified with key sequence differences in their Pleckstrin homology domains leading to differences in the recognition of lipid membranes:

* Dynamin I is expressed in neurons and neuroendocrine cells
* Dynamin II is expressed in most cell types
* Dynamin III is strongly expressed in the testis, but is also present in heart, brain, and lung tissue.[1][6]

## Pharmacology

[edit]

Small molecule inhibitors of dynamin activity have been developed, including Dynasore[11][12] and photoswitchable derivatives (Dynazo)[13] for spatiotemporal control of endocytosis with light (photopharmacology).

## Disease implications

[edit]

Mutations in Dynamin II have been found to cause dominant intermediate Charcot-Marie-Tooth disease.[14] Epileptic encephalopathy–causing de novo mutations in dynamin have been suggested to cause dysfunction of vesicle scission during synaptic vesicle endocytosis.[15]

## References

[edit]

1. ^ a b Henley, John R.; Cao, Hong; McNiven, Mark A. (December 16, 1999). "Participation of dynamin in the biogenesis of cytoplasmic vesicles". The FASEB Journal. 13 (9002): S243-7. doi:10.1096/fasebj.13.9002.S243. PMID 10619136. S2CID 24401725.
2. ^ a b Hinshaw, J. "Research statement, Jenny E. Hinshaw, Ph.D." Archived 2021-07-15 at the Wayback Machine National Institute of Diabetes & Digestive & Kidney Diseases, Laboratory of Cell Biochemistry and Biology. Accessed 19 March 2013.
3. ^ a b Urrutia R, Henley JR, Cook T, McNiven MA (January 1997). "The dynamins: redundant or distinct functions for an expanding family of related GTPases?". Proceedings of the National Academy of Sciences of the United States of America. 94 (2): 377–384\. Bibcode:1997PNAS...94..377U. doi:10.1073/pnas.94.2.377. PMC 34135. PMID 9012790.
4. ^ Thoms S, Erdmann R (October 2005). "Dynamin-related proteins and Pex11 proteins in peroxisome division and proliferation". The FEBS Journal. 272 (20): 5169–5181\. doi:10.1111/j.1742-4658.2005.04939.x. PMID 16218949.
5. ^ Hinshaw JE, Schmid SL (March 1995). "Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding". Nature. 374 (6518): 190–192\. Bibcode:1995Natur.374..190H. doi:10.1038/374190a0. PMID 7877694. S2CID 4365628.
6. ^ a b c Praefcke GJ, McMahon HT (February 2004). "The dynamin superfamily: universal membrane tubulation and fission molecules?". Nature Reviews. Molecular Cell Biology. 5 (2): 133–147\. doi:10.1038/nrm1313. PMID 15040446. S2CID 6305282.
7. ^ Sundborger AC, Fang S, Heymann JA, Ray P, Chappie JS, Hinshaw JE (August 2014). "A dynamin mutant defines a superconstricted prefission state". Cell Reports. 8 (3): 734–742\. doi:10.1016/j.celrep.2014.06.054. PMC 4142656. PMID 25088425.
8. ^ a b Kong L, Sochacki KA, Wang H, Fang S, Canagarajah B, Kehr AD, et al. (August 2018). "Cryo-EM of the dynamin polymer assembled on lipid membrane". Nature. 560 (7717): 258–262\. Bibcode:2018Natur.560..258K. doi:10.1038/s41586-018-0378-6. PMC 6121775. PMID 30069048.
9. ^ Mattila JP, Shnyrova AV, Sundborger AC, Hortelano ER, Fuhrmans M, Neumann S, et al. (August 2015). "A hemi-fission intermediate links two mechanistically distinct stages of membrane fission". Nature. 524 (7563): 109–113\. Bibcode:2015Natur.524..109M. doi:10.1038/nature14509. PMC 4529379. PMID 26123023.
10. ^ Roux A, Uyhazi K, Frost A, De Camilli P (May 2006). "GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission". Nature. 441 (7092): 528–531\. Bibcode:2006Natur.441..528R. doi:10.1038/nature04718. PMID 16648839. S2CID 4413887.
11. ^ Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T (June 2006). "Dynasore, a cell-permeable inhibitor of dynamin". Developmental Cell. 10 (6): 839–850\. doi:10.1016/j.devcel.2006.04.002. PMID 16740485.
12. ^ Eschenburg S, Reubold TF (November 2018). "Modulation of dynamin function by small molecules". Biological Chemistry. 399 (12): 1421–1432\. doi:10.1515/hsz-2018-0257. PMID 30067507. S2CID 51895475.
13. ^ Camarero N, Trapero A, Pérez-Jiménez A, Macia E, Gomila-Juaneda A, Martín-Quirós A, et al. (September 2020). "Correction: Photoswitchable dynasore analogs to control endocytosis with light". Chemical Science. 11 (35): 9712. doi:10.1039/D0SC90189J. PMC 7495901. PMID 33016959.
14. ^ Züchner S, Noureddine M, Kennerson M, Verhoeven K, Claeys K, De Jonghe P, et al. (March 2005). "Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease". Nature Genetics. 37 (3): 289–294\. doi:10.1038/ng1514. PMID 15731758. S2CID 19191581.
15. ^ Dhindsa RS, Bradrick SS, Yao X, Heinzen EL, Petrovski S, Krueger BJ, et al. (June 2015). "Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis". Neurology. Genetics. 1 (1): e4. doi:10.1212/01.NXG.0000464295.65736.da. PMC 4821085. PMID 27066543.

## External links

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Wikimedia Commons has media related to Dynamins.

* Dynamins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

Membrane protein: vesicular transport proteins (TC 1F)

Synaptic vesicle|

| SNARE|

| Q-SNARE|

* SNAP25
* SNAP29

* Syntaxin
* STX1A
* STX1B
* STX2
* STX3
* STX4
* STX5
* STX6
* STX7
* STX8
* STX10
* STX11
* STX12
* STX16
* STX17
* STX18
* STX19

* Munc-18: STXBP1
* STXBP2
* STXBP3
* STXBP4
* STXBP5
* STXBP6

|

R-SNARE|

* Synaptobrevin/VAMP: VAMP1
* VAMP2
* VAMP3

Synaptotagmin|

* SYT1
* SYT2
* SYT3
* SYT4
* SYT5
* SYT6
* SYT7
* SYT8
* SYT9
* SYT10
* SYT11
* SYT12
* SYT13
* SYT14
* SYT15
* SYT16
* SYT17

Other|

* Synaptophysin
* Synapsin

* Small GTPase: RAB3A

COPI|

* Coatomer
* COPA
* COPB1
* COPB2
* COPD/Archain
* COPE
* COPG
* COPG2
* COPZ1
* COPZ2

* Small GTPase: ARF

COPII|

* Coatomer
* SEC23A/SEC24A
* SEC13/SEC31

* Small GTPase: SAR1A

RME/Clathrin|

* CLTA
* CLTB
* CLTC

Caveolae|

* Caveolin (CAV1
* CAV2
* CAV3)

Other/ungrouped|

| Vesicle formation|

| Adaptor protein complex 1:|

* AP1AR
* AP1B1
* AP1G1
* AP1G2
* AP1M1
* AP1M2
* AP1S1
* AP1S2
* AP1S3

|

Adaptor protein complex 2:|

* AP2A1
* AP2A2
* AP2B1
* AP2M1
* AP2S1

Adaptor protein complex 3:|

* AP3B1
* AP3B2
* AP3D1
* AP3M1
* AP3M2
* AP3S1
* AP3S2

Adaptor protein complex 4:|

* AP4B1
* AP4E1
* AP4M1
* AP4S1

* LMAN1

* LYST

BLOC-1:|

* DTNBP1
* BLOC153

BLOC-2:|

* HPS3
* HPS5
* HPS6

BLOC-3:|

* HPS1
* HPS4

Coats:|

* Retromer
* TIP47

Small GTPase|

* Dynamin
* DNM1
* DNM2
* DNM3

Other|

* EHD protein family: EHD1
* EHD2
* EHD3
* EHD4

* Sorting nexins

* Vacuolar protein sorting: VPS13B
* VPS33B

* SYNRG

See also vesicular transport protein disorders

* v
* t
* e

Proteins of the cytoskeleton

Human|

| Microfilaments
and ABPs|

| Myofilament|

| Actins|

* A1
* A2
* B
* C1
* G1
* G2

|

Myosins|

* I
* MYO1A
* MYO1B
* MYO1C
* MYO1D
* MYO1E
* MYO1F
* MYO1G
* MYO1H)
* II
* MYH1
* MYH2
* MYH3
* MYH4
* MYH6
* MYH7
* MYH7B
* MYH8
* MYH9
* MYH10
* MYH11
* MYH13
* MYH14
* MYH15
* MYH16
* III
* MYO3A
* MYO3B
* V
* MYO5A
* MYO5B
* MYO5C
* VI
* MYO6
* VII
* MYO7A
* MYO7B
* IX
* MYO9A
* MYO9B
* X
* MYO10
* XV
* MYO15A
* XVIII
* MYO18A
* MYO18B
* LC
* MYL1
* MYL2
* MYL3
* MYL4
* MYL5
* MYL6
* MYL6B
* MYL7
* MYL9
* MYLIP
* MYLK
* MYLK2
* MYLL1

Other|

* Tropomodulin
* 1
* 2
* 3
* 4
* Troponin
* T 1 2 3
* C 1 2
* I 1 2 3
* Tropomyosin
* 1
* 2
* 3
* 4

* Actinin
* 1
* 2
* 3
* 4
* Arp2/3 complex
* actin depolymerizing factors
* Cofilin
* 1
* 2
* Destrin
* Gelsolin
* Profilin
* 1
* 2
* Titin

Other|

* Wiskott–Aldrich syndrome protein
* Fibrillin
* Filamin
* FLNA
* FLNB
* FLNC
* Espin
* TRIOBP

Intermediate
filaments|

| Type 1/2
(Keratin,
Cytokeratin)|

| Epithelial keratins
(soft alpha-keratins)|

* type I/chromosome 17
* 9
* 10
* 12
* 13
* 14
* 15
* 16
* 17
* 19
* 20
* chromosome 12
* 18
* none
* 21

* type II/chromosome 12
* 1
* 2A
* 3
* 4
* 5
* 6A
* 6B
* 6C
* 7
* 8

|

Hair keratins
(hard alpha-keratins)|

* type I/chromosome 17
* 31
* 32
* 33A
* 33B
* 34
* 35
* 36
* 37
* 38

* type II/chromosome 12
* 81
* 82
* 83
* 84
* 85
* 86

Ungrouped alpha|

* chromosome 17
* 23
* 24
* 25
* 26
* 27
* 28
* 39
* 40

* chromosome 12
* 71
* 72
* 73
* 74
* 75
* 76
* 77
* 78
* 79
* 80

Not alpha|

* Beta-keratin

Type 3|

* Desmin
* GFAP
* Peripherin
* Vimentin

Type 4|

* Internexin
* Nestin
* Neurofilament
* NEFL
* NEFM
* NEFH
* Synemin
* Syncoilin

Type 5|

* Nuclear lamins: A/C
* B1
* B2

Microtubules
and MAPs|

| Tubulins|

* TUBA1A
* TUBA1B
* TUBA1C
* TUBA3C
* TUBA3D
* TUBA3E
* TUBA4A
* TUBA8
* TUBB
* TUBB1
* TUBB2A
* TUBB2B
* TUBB2C
* TUBB3
* TUBB4
* TUBB4Q
* TUBB6
* TUBB8
* TUBG1
* TUBG2
* TUBGCP2
* TUBGCP3
* TUBGCP4
* TUBGCP5
* TUBGCP6
* TUBD1
* TUBE1

|

MAPs|

* EB1
* EB2
* EB3
* MAP1A
* MAP1B
* MAP2
* MAP4

Kinesins|

* KIF1A
* KIF1B
* KIF2A
* KIF2C
* KIF3B
* KIF3C
* KIF4A
* KIF4B
* KIF5A
* KIF5B
* KIF5C
* KIF6
* KIF7
* KIF9
* KIF11
* KIF12
* KIF13A
* KIF13B
* KIF14
* KIF15
* KIF16B
* KIF17
* KIF18A
* KIF18B
* KIF19
* KIF20A
* KIF20B
* KIF21A
* KIF21B
* KIF22
* KIF23
* KIF24
* KIF25
* KIF26A
* KIF26B
* KIF27
* KIFC1
* KIFC2
* KIFC3

Dyneins|

* axonemal: DNAH1
* DNAH2
* DNAH3
* DNAH5
* DNAH6
* DNAH7
* DNAH8
* DNAH9
* DNAH10
* DNAH11
* DNAH12
* DNAH13
* DNAH14
* DNAH17
* DNAI1
* DNAI2
* DNALI1
* DNAL1
* DNAL4

* cytoplasmic: DYNC1H1
* DYNC2H1
* DYNC1I1
* DYNC1I2
* DYNC1LI1
* DYNC1LI2
* DYNC2LI1
* DYNLL1
* DYNLL2
* DYNLRB1
* DYNLRB2
* DYNLT1
* DYNLT3

Microtubule organising proteins|

* CAMSAP1
* CAMSAP2
* CAMSAP3
* Centrin 1
* Centrin 2
* Centrin 3
* PCM1

Microtubule severing proteins|

* Katanin
* Spastin

Other|

* Tau protein
* Dynactin
* DCTN1
* Stathmin
* Tektin
* TEKT1
* TEKT2
* TEKT3
* TEKT4
* TEKT5
* Dynamin
* DNM1
* DNM2
* DNM3

Catenins|

* Alpha catenin
* Beta catenin
* APC
* Plakoglobin (gamma catenin)
* Delta catenin
* GAN

Membrane|

* Dystrophin
* Dystroglycan
* Utrophin
* Ankyrin
* ANK1
* ANK2
* ANK3
* Spectrin
* SPTA1
* SPTAN1
* SPTB
* SPTBN1
* SPTBN2
* SPTBN4
* SPTBN5

Other|

* Plakins
* Corneodesmosin
* Desmoplakin
* Dystonin
* Envoplakin
* MACF1
* Periplakin
* Plectin
* Talin
* TLN1
* Vinculin
* Plakophilin
* PKP1
* PKP2
* ACF7
* PLEKHA7

Nonhuman|

* Major sperm proteins
* Prokaryotic cytoskeleton
* Crescentin
* FtsZ
* MreB
* ParM

See also: cytoskeletal defects

* v
* t
* e

Hydrolases: acid anhydride hydrolases (EC 3.6)

3.6.1|

* Pyrophosphatase
* Inorganic
* Thiamine
* Apyrase
* Thiamine-triphosphatase

3.6.2|

* Adenylylsulfatase
* Phosphoadenylylsulfatase

3.6.3-4: ATPase|

| 3.6.3|

| Cu++ (3.6.3.4)|

* Menkes/ATP7A
* Wilson/ATP7B

|

Ca+ (3.6.3.8)|

* SERCA
* ATP2A1
* ATP2A2
* ATP2A3
* Plasma membrane
* ATP2B1
* ATP2B2
* ATP2B3
* ATP2B4
* SPCA
* ATP2C1
* ATP2C2

Na+/K+ (3.6.3.9)|

* ATP1A1
* ATP1A2
* ATP1A3
* ATP1A4
* ATP1B1
* ATP1B2
* ATP1B3
* ATP1B4

H+/K+ (3.6.3.10)|

* ATP4A

Other P-type ATPase|

* ATP8B1
* ATP10A
* ATP11B
* ATP12A
* ATP13A2
* ATP13A3

3.6.4|

* Dynein
* Kinesin
* Myosin
* Katanin

3.6.5: GTPase|

| 3.6.5.1: Heterotrimeric G protein|

* Gαs
* Golf
* Gαi
* GNAI1
* GNAI2
* GNAI3
* Transducin
* GNAT1
* GNAT2
* Gustducin
* GNAT3
* Gαq/11
* GNAQ
* GNA11
* Gα12/13
* GNA12
* GNA13

|

3.6.5.2: Small GTPase > Ras superfamily|

* Rho family of GTPases: Cdc42
* CDC42
* TC10
* TCL
* RhoUV
* RhoU
* RhoV
* Rac
* Rac1
* 2
* 3
* RhoG
* RhoBTB
* 1
* 2
* RhoH
* Rho
* A
* B
* C
* Rnd
* 1
* 2
* 3
* RhoDF
* RhoF
* RhoD

* other: Ras
* HRAS
* KRAS
* NRAS
* Rab
* RAB23
* RAB27
* Arf
* ARF6
* SAR1B
* ARL13B
* ARL6
* Ran
* Rheb
* Rap
* RGK

3.6.5.3: Protein-synthesizing GTPase|

* Prokaryotic
* IF-2
* EF-Tu
* EF-G
* Eukaryotic

3.6.5.5-6: Polymerization motors|

* dynamin superfamily
* Dynamin
* Guanylate-binding protein
* Mitofusin-1
* MX1 and MX2
* OPA1
* Tubulin

* v
* t
* e

Enzymes

Activity|

* Active site
* Binding site
* Catalytic triad
* Oxyanion hole
* Enzyme promiscuity
* Diffusion-limited enzyme
* Cofactor
* Enzyme catalysis

Regulation|

* Allosteric regulation
* Cooperativity
* Enzyme inhibitor
* Enzyme activator

Classification|

* EC number
* Enzyme superfamily
* Enzyme family
* List of enzymes

Kinetics|

* Enzyme kinetics
* Eadie–Hofstee diagram
* Hanes–Woolf plot
* Lineweaver–Burk plot
* Michaelis–Menten kinetics

Types|

* EC1 Oxidoreductases (list)
* EC2 Transferases (list)
* EC3 Hydrolases (list)
* EC4 Lyases (list)
* EC5 Isomerases (list)
* EC6 Ligases (list)
* EC7 Translocases (list)

Portal:

* Biology

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