Crystal structure of the RIM1α C2B domain at 1.7 Å resolution

Rong Guan, Han Dai, Diana R Tomchick, Irina Dulubova, Mischa Machius, Thomas C. Südhof, Jose Rizo-Rey

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

RIM proteins play critical roles in synaptic vesicle priming and diverse forms of presynaptic plasticity. The C-terminal C2B domain is the only module that is common to all RIMs but is only distantly related to well-studied C2 domains, and its three-dimensional structure and interactions have not been characterized in detail. Using NMR spectroscopy, we now show that N- and C-terminal extensions beyond the predicted C2B domain core sequence are necessary to form a folded, stable RIM1α C 2B domain. We also find that the isolated RIM1α C2B domain is not sufficient for previously described protein-protein interactions involving the RIM1α C-terminus, suggesting that additional sequences adjacent to the C2B domain might be required for these interactions. However, analytical ultracentrifugation shows that the RIM1α C 2B domain forms weak dimers in solution. The crystal structure of the RIM1α C2B domain dimer at 1.7 Å resolution reveals that it forms a β-sandwich characteristic of C2 domains and that the unique N- and C-terminal extensions form a small subdomain that packs against the β-sandwich and mediates dimerization. Our results provide a structural basis to understand the function of RIM C2B domains and suggest that dimerization may be a crucial aspect of RIM function.

Original languageEnglish (US)
Pages (from-to)8988-8998
Number of pages11
JournalBiochemistry
Volume46
Issue number31
DOIs
StatePublished - Aug 7 2007

Fingerprint

Reaction injection molding
Crystal structure
Dimerization
Dimers
Proteins
Synaptic Vesicles
Ultracentrifugation
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance spectroscopy
Plasticity
C2 Domains

ASJC Scopus subject areas

  • Biochemistry

Cite this

Crystal structure of the RIM1α C2B domain at 1.7 Å resolution. / Guan, Rong; Dai, Han; Tomchick, Diana R; Dulubova, Irina; Machius, Mischa; Südhof, Thomas C.; Rizo-Rey, Jose.

In: Biochemistry, Vol. 46, No. 31, 07.08.2007, p. 8988-8998.

Research output: Contribution to journalArticle

Guan, R, Dai, H, Tomchick, DR, Dulubova, I, Machius, M, Südhof, TC & Rizo-Rey, J 2007, 'Crystal structure of the RIM1α C2B domain at 1.7 Å resolution', Biochemistry, vol. 46, no. 31, pp. 8988-8998. https://doi.org/10.1021/bi700698a
Guan R, Dai H, Tomchick DR, Dulubova I, Machius M, Südhof TC et al. Crystal structure of the RIM1α C2B domain at 1.7 Å resolution. Biochemistry. 2007 Aug 7;46(31):8988-8998. https://doi.org/10.1021/bi700698a
Guan, Rong ; Dai, Han ; Tomchick, Diana R ; Dulubova, Irina ; Machius, Mischa ; Südhof, Thomas C. ; Rizo-Rey, Jose. / Crystal structure of the RIM1α C2B domain at 1.7 Å resolution. In: Biochemistry. 2007 ; Vol. 46, No. 31. pp. 8988-8998.
@article{527bf7a309b043f287838c4f051341ca,
title = "Crystal structure of the RIM1α C2B domain at 1.7 {\AA} resolution",
abstract = "RIM proteins play critical roles in synaptic vesicle priming and diverse forms of presynaptic plasticity. The C-terminal C2B domain is the only module that is common to all RIMs but is only distantly related to well-studied C2 domains, and its three-dimensional structure and interactions have not been characterized in detail. Using NMR spectroscopy, we now show that N- and C-terminal extensions beyond the predicted C2B domain core sequence are necessary to form a folded, stable RIM1α C 2B domain. We also find that the isolated RIM1α C2B domain is not sufficient for previously described protein-protein interactions involving the RIM1α C-terminus, suggesting that additional sequences adjacent to the C2B domain might be required for these interactions. However, analytical ultracentrifugation shows that the RIM1α C 2B domain forms weak dimers in solution. The crystal structure of the RIM1α C2B domain dimer at 1.7 {\AA} resolution reveals that it forms a β-sandwich characteristic of C2 domains and that the unique N- and C-terminal extensions form a small subdomain that packs against the β-sandwich and mediates dimerization. Our results provide a structural basis to understand the function of RIM C2B domains and suggest that dimerization may be a crucial aspect of RIM function.",
author = "Rong Guan and Han Dai and Tomchick, {Diana R} and Irina Dulubova and Mischa Machius and S{\"u}dhof, {Thomas C.} and Jose Rizo-Rey",
year = "2007",
month = "8",
day = "7",
doi = "10.1021/bi700698a",
language = "English (US)",
volume = "46",
pages = "8988--8998",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "31",

}

TY - JOUR

T1 - Crystal structure of the RIM1α C2B domain at 1.7 Å resolution

AU - Guan, Rong

AU - Dai, Han

AU - Tomchick, Diana R

AU - Dulubova, Irina

AU - Machius, Mischa

AU - Südhof, Thomas C.

AU - Rizo-Rey, Jose

PY - 2007/8/7

Y1 - 2007/8/7

N2 - RIM proteins play critical roles in synaptic vesicle priming and diverse forms of presynaptic plasticity. The C-terminal C2B domain is the only module that is common to all RIMs but is only distantly related to well-studied C2 domains, and its three-dimensional structure and interactions have not been characterized in detail. Using NMR spectroscopy, we now show that N- and C-terminal extensions beyond the predicted C2B domain core sequence are necessary to form a folded, stable RIM1α C 2B domain. We also find that the isolated RIM1α C2B domain is not sufficient for previously described protein-protein interactions involving the RIM1α C-terminus, suggesting that additional sequences adjacent to the C2B domain might be required for these interactions. However, analytical ultracentrifugation shows that the RIM1α C 2B domain forms weak dimers in solution. The crystal structure of the RIM1α C2B domain dimer at 1.7 Å resolution reveals that it forms a β-sandwich characteristic of C2 domains and that the unique N- and C-terminal extensions form a small subdomain that packs against the β-sandwich and mediates dimerization. Our results provide a structural basis to understand the function of RIM C2B domains and suggest that dimerization may be a crucial aspect of RIM function.

AB - RIM proteins play critical roles in synaptic vesicle priming and diverse forms of presynaptic plasticity. The C-terminal C2B domain is the only module that is common to all RIMs but is only distantly related to well-studied C2 domains, and its three-dimensional structure and interactions have not been characterized in detail. Using NMR spectroscopy, we now show that N- and C-terminal extensions beyond the predicted C2B domain core sequence are necessary to form a folded, stable RIM1α C 2B domain. We also find that the isolated RIM1α C2B domain is not sufficient for previously described protein-protein interactions involving the RIM1α C-terminus, suggesting that additional sequences adjacent to the C2B domain might be required for these interactions. However, analytical ultracentrifugation shows that the RIM1α C 2B domain forms weak dimers in solution. The crystal structure of the RIM1α C2B domain dimer at 1.7 Å resolution reveals that it forms a β-sandwich characteristic of C2 domains and that the unique N- and C-terminal extensions form a small subdomain that packs against the β-sandwich and mediates dimerization. Our results provide a structural basis to understand the function of RIM C2B domains and suggest that dimerization may be a crucial aspect of RIM function.

UR - http://www.scopus.com/inward/record.url?scp=34547738934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547738934&partnerID=8YFLogxK

U2 - 10.1021/bi700698a

DO - 10.1021/bi700698a

M3 - Article

C2 - 17630786

AN - SCOPUS:34547738934

VL - 46

SP - 8988

EP - 8998

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 31

ER -