Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bovine microtubule-associated protein-4 (MAP-4), which was previously named MAP-U, consists of an amino-terminal projection domain (N-domain) and a carboxyl-terminal microtubule-binding domain (C-domain) (Aizawa, H., Emori, Y., Murofushi, H., Kawasaki, H., Sakai, H., and Suzuki, K. (1990) J. Biol. Chem. 265, 13849-13855). The C-domain contains a region rich in proline (Pro-rich region) and a region containing four assembly-promoting sequences (AP sequence region) which is shared by MAP-2 and tau. We purified a series of truncated fragments of MAP-4 expressed in Escherichia coli. An N-domain fragment did not bind to microtubules, while a C-domain fragment promoted microtubule assembly. Both of the fragments corresponding to the Pro-rich region (P fragment) and the AP sequence region (A4 fragment) promoted tubulin polymerization, although the A4 fragment had lower activity than intact MAP-4 and P fragment. A4 fragment produced morphologically normal microtubules whereas P fragment produced abnormal microtubules such as duplex microtubules and tight bundles of microtubules with diverse diameters. We concluded that both Pro-rich and AP sequence regions take part in the promotion of tubulin polymerization, and that the former is important for the MAP to bind to microtubules with high efficiency and the latter is essential for the formation of microtubules with normal morphology.
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PMID:Functional analyses of the domain structure of microtubule-associated protein-4 (MAP-U). 203 72

Previously we reported that chymotryptic fragments of bovine adrenal 190-kDa microtubule-associated proteins (27-kDa fragment) and bovine brain tau (14-kDa fragment) contained microtubule-binding domain (Aizawa, H., Murofushi, H., Kotani, Hisanaga, S., Hirokawa, N., and Sakai, H. (1987) J. Biol. Chem. 262, 3782-3787; Aizawa, H., Kawasaki, H., Murofushi, H., Kotani, S., Suzuki, K., and Sakai, H. (1988) J. Biol. Chem. 263, 7703-7707). In order to study the structure of microtubule-binding domain of the two microtubule-associated proteins, we analyzed the amino acid sequence of the 27-kDa fragment and compared the sequence with that of the 14-kDa fragment. This revealed that 190-kDa microtubule-associated protein and tau contained at least one common sequence of 20 amino acid residues in their microtubule-binding domains. A synthetic polypeptide corresponding to the common sequence (Lys-Asn-Val-Arg-Ser-Lys-Val-Gly-Ser-Thr-Glu-Asn-Ile-Lys- His-Gln-Pro-Gly-Gly-Gly-Arg-Ala-Lys) was bound to microtubules competitively with the 190-kDa MAP. The apparent dissociation constant (KD) for the binding of the polypeptide to microtubules was estimated to be 1.8 x 10(-4) M, and the maximum binding reached 1.2 mol of the synthetic polypeptide/mol of tubulin dimer. This synthetic polypeptide increased the rate and extent of tubulin polymerization and decreased the critical concentration of tubulin for polymerization. The polypeptide-induced tubulin polymers were morphologically normal microtubules and were disassembled by cold treatment. The common sequence (termed assembly-promoting sequence) was thus identified as the active site of 190-kDa microtubule-associated protein and tau for the promotion of microtubule assembly. The reconstitution system of microtubules with this synthetic polypeptide with assembly-promoting sequence may be useful to elucidate detailed molecular mechanism of the promotion of microtubule assembly by microtubule-associated proteins.
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PMID:A common amino acid sequence in 190-kDa microtubule-associated protein and tau for the promotion of microtubule assembly. 249 69