PMID- 10600384
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20131121
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 294
IP  - 5
DP  - 1999 Dec 17
TI  - X-ray structure determination of human profilin II: A comparative structural
      analysis of human profilins.
PG  - 1271-85
AB  - Human profilins are multifunctional, single-domain proteins which directly link
      the actin microfilament system to a variety of signalling pathways via two
      spatially distinct binding sites. Profilin binds to monomeric actin in a 1:1
      complex, catalyzes the exchange of the actin-bound nucleotide and regulates actin
      filament barbed end assembly. Like SH3 domains, profilin has a surface-exposed
      aromatic patch which binds to proline-rich peptides. Various multidomain proteins
      including members of the Ena/VASP and formin families localize profilin:actin
      complexes through profilin:poly-L-proline interactions to particular cytoskeletal
      locations (e.g. focal adhesions, cleavage furrows). Humans express a basic (I)
      and an acidic (II) isoform of profilin which exhibit different affinities for
      peptides and proteins rich in proline residues. Here, we report the
      crystallization and X-ray structure determination of human profilin II to 2.2 A. 
      This structure reveals an aromatic extension of the previously defined
      poly-L-proline binding site for profilin I. In contrast to serine 29 of profilin 
      I, tyrosine 29 in profilin II is capable of forming an additional stacking
      interaction and a hydrogen bond with poly-L-proline which may account for the
      increased affinity of the second isoform for proline-rich peptides. Differential 
      isoform specificity for proline-rich proteins may be attributed to the
      differences in charged and hydrophobic residues in and proximal to the
      poly-L-proline binding site. The actin-binding face remains nearly identical with
      the exception of five amino acid differences. These observations are important
      for the understanding of the functional and structural differences between these 
      two classes of profilin isoforms.
CI  - Copyright 1999 Academic Press.
FAU - Nodelman, I M
AU  - Nodelman IM
AD  - Department of Molecular Biology, Henry H. Hoyt Laboratory, Princeton University, 
      Princeton, NJ 08544, USA.
FAU - Bowman, G D
AU  - Bowman GD
FAU - Lindberg, U
AU  - Lindberg U
FAU - Schutt, C E
AU  - Schutt CE
LA  - eng
SI  - PDB/1D1J
GR  - GM08309/GM/NIGMS NIH HHS/United States
GR  - GM44038/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Acids)
RN  - 0 (Actins)
RN  - 0 (Contractile Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (PFN1 protein, human)
RN  - 0 (PFN2 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Profilins)
RN  - 0 (Protein Isoforms)
RN  - 25191-13-3 (polyproline)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Acids/chemistry/metabolism
MH  - Actins/metabolism
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Binding Sites
MH  - *Contractile Proteins
MH  - Crystallization
MH  - Crystallography, X-Ray
MH  - Cysteine/metabolism
MH  - Humans
MH  - Hydrogen Bonding
MH  - Isoelectric Point
MH  - Microfilament Proteins/*chemistry/metabolism
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Peptides/metabolism
MH  - Profilins
MH  - Protein Conformation
MH  - Protein Isoforms/chemistry/metabolism
MH  - Sequence Alignment
MH  - Static Electricity
MH  - Structure-Activity Relationship
MH  - Substrate Specificity
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1006/jmbi.1999.3318 [doi]
AID - S0022-2836(99)93318-1 [pii]
PST - ppublish
SO  - J Mol Biol. 1999 Dec 17;294(5):1271-85. doi: 10.1006/jmbi.1999.3318.