Synaptobrevin
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Synaptobrevins (''synaptobrevin isotypes 1-2'') are small
integral membrane proteins An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signi ...
of
secretory vesicle 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
s with
molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
of 18
kilodalton The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at ...
(kDa) that are part of the
vesicle-associated membrane protein Vesicle associated membrane proteins (VAMP) are a family of SNARE proteins with similar structure, and are mostly involved in vesicle fusion. * VAMP1 and VAMP2 proteins known as synaptobrevins are expressed in brain and are constituents of t ...
(VAMP) family. Synaptobrevin is one of the SNARE proteins involved in formation of the SNARE complexes.


Structure

Out of four α-helices of the core SNARE complex one is contributed by synaptobrevin, one by
syntaxin Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis. Domains Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxin ...
, and two by
SNAP-25 Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (''N''-ethylmaleimide-sensitive factor) Attachment Protein Receptor ( t-SNARE) protein encoded by the ''SNAP25'' gene found on chromosome 20p12.2 in humans. SNAP-25 is a com ...
(in neurons).


Function

SNARE proteins are the key components of the molecular machinery that drives fusion of membranes in
exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
. Their function however is subject to fine-tuning by various regulatory proteins collectively referred to as ''SNARE masters''.


Classification

In the Q/R
nomenclature Nomenclature (, ) is a system of names or terms, or the rules for forming these terms in a particular field of arts or sciences. The principles of naming vary from the relatively informal naming conventions, conventions of everyday speech to the i ...
for organizing SNARE proteins, VAMP/synaptobrevin family members are classified as R-SNAREs, so named for the presence of an
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
at a specific location within the
primary sequence Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length sc ...
of the protein (as opposed to the SNAREs of the target membrane, which contain a
glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...
and are so named
Q-SNARE SNARE proteins – " SNAP REceptor" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate vesicle ...
s). Synaptobrevin is classified as a V-SNARE in the V/T nomenclature, an alternative classification scheme in which SNAREs are classified as V-SNAREs and T-SNAREs for their localization to
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
and target membranes, respectively.Juan S. Bonifacino and Benjamin S. Glick. "The Mechanisms of Vesicle Budding and Fusion." Cell, Vol. 116, 153–166, January 23, 2004,


Clinical significance

Synaptobrevin is degraded by
tetanospasmin Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of ''Clostridium tetani'' in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally ...
, a protein derived from the bacterium ''
Clostridium tetani ''Clostridium tetani'' is a common soil bacterium and the causative agent of tetanus. Vegetative cells of ''Clostridium tetani'' are usually rod-shaped and up to 2.5 μm long, but they become enlarged and tennis racket- or drumstick-shaped when ...
'', which causes
tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
. A related bacterium, ''
Clostridium botulinum ''Clostridium botulinum'' is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum. The botulinum toxin can cause botulism, a severe flaccid paralytic disease in humans an ...
'', produces the
botulinum toxin Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromusc ...
. Various botulinum toxin serotypes exist that each cleave specific peptide bonds of specific neuronal SNARE proteins, and synaptobrevin is this target protein for several of the serotypes.


Human proteins containing this domain

SEC22A; SEC22B; SYBL1; VAMP1;
VAMP2 Vesicle-associated membrane protein 2 (VAMP2) is a protein that in humans is encoded by the ''VAMP2'' gene. Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein ...
;
VAMP3 Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the ''VAMP3'' gene. Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein are the main components of a protein complex involved i ...
;
VAMP4 Vesicle-associated membrane protein 4 is a protein that in humans is encoded by the ''VAMP4'' gene. Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex inv ...
; VAMP5; VAMP8; YKT6;


References and notes


External links

*
Myobloc (rimabotulinumtoxinB) Prescribing Information
{{Vesicular transport proteins Protein domains Protein families Single-pass transmembrane proteins