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C D Surridge

Publications and source records attributed to C D Surridge.

7 recordsLinked to original sources
PubMed1995

The phosphatidylinositol-binding site of microtubule-associated protein MAP2.

Recent evidence [Surridge and Burns, Biochemistry (1994) 33, 8051-8057] on the interaction of native and recombinant tau, recombinant MAP2c, and native MAP2 with vesicles prepared from phosphatidylinositol (PtdIns) and other phospholipids demonstrate that MAP2 differs from MAP2c and from tau in having a high-affinity PtdIns-binding site. The location of this site within the MAP2-specific insert peptide, coupled with considerations of the nature of the MAP2 tubulin-binding site, suggests that PtdIns-binding induces a conformational change which alters the MAP2 tubulin-binding domain. Furthermore, the restricted cellular distribution of MAP2 implies that the MAP2:PtdIns interaction may play a central role in modulating the dendritic cytoskeleton.

Animals↗
PubMed1994

The difference in the binding of phosphatidylinositol distinguishes MAP2 from MAP2C and Tau.

The interactions of bovine brain MAP2 and tau, recombinant murine MAP2C, and recombinant human tau with phosphatidylinositol vesicles yield apparent Kd values of 51 +/- 6 nM, 2.4 +/- 0.6 microM, 1.4 +/- 0.1 microM, and 1.6 +/- 0.2 microM, respectively. Examinations of the binding of MAP2 and/or MAP2C to phosphatidylcholine vesicles doped with phosphatidylinositol or to phosphatidylserine vesicles and of thrombin-digested MAP2C to phosphatidylinositol vesicles demonstrates that the observed high affinity of the MAP2: phosphatidylinositol binding is due to the contributions of two separate interactions. A low-affinity site (Kd = 1.5-2.5 microM) is located within the C-terminal domain and affects the nonspecific interaction of MAP2, MAP2C, and tau with anionic phospholipids. The second site, with an apparent Kd of 221 +/- 25 nM, is located within the MAP2-specific peptide, which is eliminated from MAP2C by differential gene splicing. It is proposed that the high affinity of MAP2 for phosphatidylinositol contributes to the spatial and temporal regulation of the dendritic cytoskeleton.

Alternative Splicing↗
PubMed1994

Functional role of a consensus peptide which is common to alpha-, beta-, and gamma-tubulin, to actin and centractin, to phytochrome A, and to the TCP1 alpha chaperonin protein.

The TRiC (TCP1 Ring Complex) chaperonin complex participates in the functional folding of actin, centractin, alpha-, beta-, gamma-tubulin, and phytochrome. Each of the cytoskeletal proteins contain a peptide, RK(A,C,T)F/KRAF, located towards the C-terminus, which is homologous to a TCP1 alpha peptide, while the equivalent phytochrome peptide (RLKAF in certain isoforms) is very similar to the KLRAF peptide of TCP1 alpha. We propose that this TCP1 alpha peptide binds to the nascent polypeptides as they emerge from the ribosome, that this binding restricts the folding pathway, and that the TCP1 alpha peptide is subsequently displaced by the synthesis of the consensus peptide. This hypothesis is strongly supported by the crystallographic structure of actin.

Actins↗
PubMed1993

Should the tubulins be members of the GTPase superfamily?

The beta-subunit of the alpha/beta tubulin heterodimer resembles other members of the GTPase superfamily in that: it binds GTP, the GTP is hydrolysed to GDP on microtubule assembly and this induces a conformational change; it exhibits a similar nucleotide stereospecificity; aluminium and beryllium fluorides inhibit this hydrolysis-dependent conformational change; and beta-tubulin contains peptides which are similar to the consensus motifs characteristic of the GTPase superfamily proteins. By contrast, UV photo-cross-linking and other binding studies have identified peptides which may contribute to the GTP-binding site but which are absent from the GTPase superfamily proteins. We suggest that beta-tubulin has a 'dual personality', with the characteristics of the GTP-binding site depending upon the precise conformation of the protein and upon whether the experimental assays probe nucleotide binding or the hydrolytic mechanism. We suggest that the hydrolytic mechanism of beta-tubulin resembles that of the other members of the GTPase superfamily, although the differences within the consensus motifs dictate that the architecture of the GTP pocket cannot be identical.

Amino Acid Sequence↗
PubMed1992

Phosphatidylinositol inhibits microtubule assembly by binding to microtubule-associated protein 2 at a single, specific, high-affinity site.

The effects of various anionic phospholipids on the in vitro assembly of MAP2/tubulin microtubules has been examined. We show that the potency to inhibit is related to the polarity of the phospholipids and that this is consistent with a mode of action involving the sequencing of microtubule-associated proteins (MAPs) by nonspecific electrostatic interactions. The inhibitory potency of phosphatidylinositol (PI) is, however, considerably larger than predicted by this model. The effects of PI on MAP2/tubulin microtubule assembly have therefore been examined in greater detail by preparing phosphatidylcholine (PC) liposomes doped with increasing amounts of PI. We show that when the PI is sufficiently dispersed by dilution with PC, it inhibits microtubule assembly by binding to MAP2 with an apparent stoichiometry, after correction for the bilamellar nature of the liposomes, of 1:1 mol.mol-1 PI:MAP2. Furthermore, we show that the Kd of this interaction is in the submicromolar range.

Animals↗
PubMed1991

Identification of an inhibitor of microtubule assembly present in juvenile brain which displays a novel mechanism of action involving suppression of self-nucleation.

An inhibitor of microtubule assembly has been identified and partially purified from microtubule-depleted brain extracts from day-old chicks and 4-month-old calf. This inhibitor suppresses the self-nucleation of microtubules in vitro with minimal effect upon the final extent of assembly. It may have a developmental role in vivo as it is not detected in adult brain from either cattle or rabbit.

Ammonium Sulfate↗